Nuclear localization of beta-catenin involved in precancerous change in oral leukoplakia.

Mol Cancer. 2007;6:62

Authors: Ishida K, Ito S, Wada N, Deguchi H, Hata T, Hosoda M, Nohno T

BACKGROUND: Oral leukoplakia is a precancerous change developed in the oral mucosa, and the mechanism that oral leukoplakia becomes malignant through atypical epithelium is not known. Here we compared the beta-catenin expression detected by immunohistochemical staining in the normal oral epithelium and in the oral leukoplakia with or without dysplasia. RESULTS: The normal oral epithelium showed beta-catenin expression only in the cell membrane, but not in the nuclei. In the oral leukoplakia without dysplasia, 7 out of 17 samples (41%) showed beta-catenin expression in the cell membrane, and 5 samples (29%) showed expression in the nuclei. In the oral leukoplakia with dysplasia, nuclear expression of beta-catenin was shown in 11 out of 12 samples (92%). Incidence of nuclear beta-catenin expression was significantly different between dysplasia and normal oral epithelium (P < 0.01), and also between oral leukoplakia with dysplasia and those without dysplasia (P < 0.01). Wnt3 expression was detected in the epithelial cell membrane or cytoplasm in oral leukoplakia where nuclear expression of beta-catenin was evident, but not in epithelial cells without nuclear expression of beta-catenin. CONCLUSION: The components of canonical Wnt pathway, such as Wnt3, beta-catenin, and cyclin D1, were detected, implying that this pathway is potentially involved in the progression of dysplasia in oral leukoplakia.

PMID: 17922924 [PubMed - in process]

Comparison of staining of mitotic figures by haematoxylin and eosin-and crystal violet stains, in oral epithelial dysplasia and squamous cell carcinoma.

Indian J Dent Res. 2007 Jul-Sep;18(3):101-5

Authors: Ankle MR, Kale AD, Charantimath S

Mitosis of cells gives rise to tissue integrity. Defects during mitosis bring about abnormalities. Excessive proliferation of cells due to increased mitosis is one such outcome, which is the hallmark in precancer and cancer. The localization of proliferating cells or their precursors may not be obvious and easy. Establishing an easy way to distinguish these mitotic cells will help in grading and understanding their biological potential. Although immunohistochemistry is an advanced method in use, the cost and time factor makes it less feasible for many laboratories. Selective histochemical stains like toluidine blue, giemsa and crystal violet have been used in tissues including the developing brain, neural tissue and skin. AIM OF THE STUDY: 1) To compare the staining of mitotic cells in haematoxylin and eosin with that in crystal violet. 2) To compare the number of mitotic figures present in normal oral mucosa, epithelial dysplasia and oral squamous cell carcinoma in crystal violet-stained sections with that in H and E-stained sections. MATERIALS AND METHODS: Ten tissues of normal oral mucosa and 15 tissues each of oral epithelial dysplasia seen in tobacco-associated leukoplakia and squamous cell carcinoma were studied to evaluate the selectivity of 1% crystal violet for mitotic figures. The staining was compared with standard H and E staining. Statistical analysis was done using Mann-Whitney U test. RESULTS: A statistically significant increase in the mean mitotic count was observed in crystal violet-stained sections of epithelial dysplasia as compared to the H and E-stained sections (p=0.0327). A similar increase in the mitotic counts was noted in crystal violet-stained sections of oral squamous cell carcinoma as compared to the H and E-stained sections.(p=0.0443). No significant difference was found in the mitotic counts determined in dysplasia or carcinoma by either the crystal violet (p=0.4429) or the H and E-staining techniques (p=0.2717). CONCLUSION: One per cent crystal violet provides a definite advantage over the H and E-stained sections in selectively staining the mitotic figures.

PMID: 17687171 [PubMed - indexed for MEDLINE]

Zinsser-Cole-Engmann syndrome.

Indian J Dermatol Venereol Leprol. 2001 Jan-Feb;67(1):35-6

Authors: Masood Q, Manzoor S, Hussain I

Zinser-Cole-Engmann syndrome is a rare syndrome characterized by atrophy and pigmentation of skin, nail dystrophy and oral leukoplakia. Here we report a case of this rare entity.

PMID: 17664699 [PubMed]

Prevalence of oral hairy leukoplakia and epithelial infection by Epstein-Barr virus in pregnant women and diabetes mellitus patients--cytopathologic and molecular study.

Mem Inst Oswaldo Cruz. 2007 May;102(2):159-64

Authors: Milagres A, Dias EP, Tavares Ddos S, Cavalcante RM, Dantas VA, de Oliveira SP, Leite JP

Oral hairy leukoplakia (OHL) is generally reported in patients with severe immunosuppression, except for a few cases in individuals with moderate degree of immunodeficiency. It is a white lesion that appears mainly in the lateral border of the tongue, caused by Epstein-Barr virus (EBV). The nuclear changes caused by EBV (Cowdry A inclusion, ground glass and nuclear beading), observed in cytopathology, are specific and enough for the definitive diagnosis of OHL, independent of the identification of the virus. Here we investigated the prevalence of OHL and the presence of EBV-DNA in the lateral borders of the tongue from 90 pregnant women, 90 diabetes mellitus (DM) patients, 30 healthy individuals (negative group) and 30 HIV+ with OHL (positive group). Smears were analyzed by cytopathology and polymerase chain reaction (PCR). A case of subclinical OHL and candidiasis was identificated in a DM patient by cytopathologic analysis. PCR results demonstrated EBV-DNA in 65% of the pregnant women, in 35% of DM patients, and in 20% of the healthy individuals. We concluded that DM patients can develop OHL with a low prevalence. Furthermore, the prevalence of the EBV in lateral border of the tongue is larger in pregnant women than in healthy individuals.

PMID: 17426879 [PubMed - indexed for MEDLINE]

Does a clinico-pathological correlation exist between tonsillar carcinoma and oral proliferative verrucous leukoplakia?

Minerva Stomatol. 2007 Mar;56(3):153-4

Authors: Capodiferro S, Maiorano E, Scully C, Favia G

PMID: 17327820 [PubMed - indexed for MEDLINE]

Common oral lesions: Part II. Masses and neoplasia.

Am Fam Physician. 2007 Feb 15;75(4):509-12

Authors: Gonsalves WC, Chi AC, Neville BW

Certain common oral lesions appear as masses, prompting concern about oral carcinoma. Many are benign, although some (e.g., leukoplakia) may represent neoplasia or cancer. Palatal and mandibular tori are bony protuberances and are benign anomalies. Oral pyogenic granulomas may appear in response to local irritation, trauma, or hormonal changes of pregnancy. Mucoceles represent mucin spillage into the oral soft tissues resulting from rupture of a salivary gland duct. Oral fibromas form as a result of irritation or masticatory trauma, especially along the buccal occlusal line. Oral cancer may appear clinically as a subtle mucosal change or as an obvious mass. Oral leukoplakia is the most common premalignant oral lesion. For persistent white or erythematous oral lesions, biopsy should be performed to rule out neoplastic change or cancer. Most oral cancers are squamous cell carcinomas. Tobacco and heavy alcohol use are the principal risk factors for oral cancer. Family physicians should be able to recognize these lesions and make appropriate referrals for biopsy and treatment.

PMID: 17323711 [PubMed - indexed for MEDLINE]

Prevalence of oral lesions in relation to habits: Cross-sectional study in South India.

Indian J Dent Res. 2006 Jul-Sep;17(3):121-5

Authors: Saraswathi TR, Ranganathan K, Shanmugam S, Sowmya R, Narasimhan PD, Gunaseelan R

BACKGROUND: Smoking, drinking and chewing tobacco product, common habits in India have been positively associated with oral lesions. No study has been conducted in this part of Tamilnadu regarding the prevalence of oral lesions in relation to habits. METHODS: A hospital based cross-sectional study was carried out at Ragas Dental College, Chennai. Already existing data of two thousand and seventeen consecutive patients from sub-urban areas of Chennai, who attended the outpatient department, at Ragas Dental College, for dental complaints during a period of three months in 2004, who underwent oral examination and interviewer based questionnaire was used. RESULTS: Oral soft tissue lesions were found in 4.1% of the study subjects. The prevalence of leukoplakia, OSF and oral lichen planus was 0.59%, 0.55%, and 0.15% respectively. The prevalence of smoking, drinking alcoholic beverages and chewing was 15.02%, 8.78% and 6.99% respectively. Smoking and chewing were significant predictors of leukoplakia in this population. DISCUSSION: The prevalence of leukoplakia, OSF and oral lichen planus in our study population is similar to those found in other populations. The prevalence of consumption of alcoholic beverages in our study population was higher when compared to the Indian National Sample Survey study. However the prevalence of smoking and chewing was found to be lower. Smokers were more likely to develop smoker's melanosis compared to other lesions. Among those who consumed alcoholic beverages alone, the prevalence of leukoplakia was higher compared to other lesions. OSF was the most prevalent lesion among those who chewed panmasala or gutkha or betel quid with or without tobacco.

PMID: 17176828 [PubMed - indexed for MEDLINE]

Circulating immune complexes and trace elements (Copper, Iron and Selenium) as markers in oral precancer and cancer : a randomised, controlled clinical trial.

Head Face Med. 2006;2:33

Authors: Khanna SS, Karjodkar FR

AIM: To evaluate the levels of circulating immune complexes, trace elements (copper, iron and selenium) in serum of patients with oral submucous fibrosis (OSMF), oral leukoplakia (L), and oral squamous cell carcinoma (SCC), analyze the alteration and identify the best predictors amongst these parameters for disease occurrence and progression. METHODS: Circulating immune complexes (CIC) were estimated using 37.5% Polyethylene Glycol 6000(PEG) serum precipitation. Serum estimation of copper (Cu), Iron (Fe) and selenium (Se) was done using the Oxalyl Dihydrazide method, Colorimetric Dipyridyl method and the Differential Pulse Cathodic Stripping Voltametry respectively. RESULTS: The data analysis revealed increased circulating immune complex levels in the precancer and cancer patients. Serum copper levels showed gradual increase from precancer to cancer patients. However, serum iron levels were decreased significantly in the cancer group. Selenium levels showed marked decrease in the cancer group. Among CIC, serum, copper, iron and selenium the best predictors for the occurrence of lesions were age, serum iron, CIC, serum selenium in the decreasing order. CONCLUSION: The present study shows that these immunological and biological markers may be associated with the pathogenesis of oral premalignant and malignant lesions and their progressions. Concerted efforts would, therefore, help in early detection, management, and monitoring the efficacy of treatment.

PMID: 17040577 [PubMed]

Expression of concern - Sudbo J. Novel management of oral cancer: a paradigm of predictive oncology. Clin Med Res 2004;2:233-242.

Clin Med Res. 2006 Sep;4(3):160

Authors: Dart RA, Salzman-Scott SA

PMID: 16988092 [PubMed - indexed for MEDLINE]

Prevalence of oral hairy leukoplakia in 120 pediatric patients infected with HIV-1.

Braz Oral Res. 2006 Apr-Jun;20(2):103-7

Authors: Dias EP, Israel MS, Silva Junior A, Maciel VA, Gagliardi JP, Oliveira RH

Oral hairy leukoplakia (OHL) is an EBV (Epstein-Barr virus) opportunistic infection found in HIV-infected patients. It is an asymptomatic lesion that has an important prognostic value in AIDS. Differently from what takes place with HIV adult patients, OHL has been described in the literature as having a very small prevalence in pediatric patients. Therefore, the aim of this study was to investigate the prevalence of OHL in HIV pediatric patients using cytopathology. The sample consisted of 120 patients who were submitted to oral examination and had material scraped from both sides of their tongues. The diagnostic criterion was based on the identification of nuclear alterations. Clinical OHL was identified in two (1.67%) patients. The cytopathology revealed twenty (16.7%) cases of subclinical OHL. Our results show that in pediatric patients the prevalence of OHL may be larger than that described in the literature.

PMID: 16878201 [PubMed - indexed for MEDLINE]

Oral cancer education in dental schools: knowledge and experience of Nigerian undergraduate students.

J Dent Educ. 2006 Jun;70(6):676-80

Authors: Uti OG, Fashina AA

The objective of this study was to determine the knowledge and experiences of clinical dental students of the College of Medicine, University of Lagos, Nigeria related to the management and prevention of oral malignancy and premalignancy. A self-administered questionnaire was distributed to all clinical dental students. Most of the students (87.7 percent; n=57) had witnessed at least a patient with oral malignancy, while 61.5 percent (n=40) had witnessed or examined a patient with oral premalignancy. While 61.5 percent of the students had observed biopsies of malignant and premalignant lesions, only 13.8 percent (n=9) had ever performed one under supervision. All the respondents believed that oral malignancy is always or sometimes associated with pain, and most of the students were more familiar with the late signs of oral malignancy than the early signs. Almost two-thirds (64.6 percent) of the respondents believed that oral screening programs were effective for early diagnosis and management of oral malignancies. This study revealed a need for a more structured teaching program with increased emphasis on the early signs and symptoms of oral malignancies and involvement of the students in the examination and biopsies of malignant and premalignant lesions.

PMID: 16741136 [PubMed - indexed for MEDLINE]

Fenretinide activity in retinoid-resistant oral leukoplakia.

Clin Cancer Res. 2006 May 15;12(10):3109-14

Authors: Lippman SM, Lee JJ, Martin JW, El-Naggar AK, Xu X, Shin DM, Thomas M, Mao L, Fritsche HA, Zhou X, Papadimitrakopoulou V, Khuri FR, Tran H, Clayman GL, Hittelman WN, Hong WK, Lotan R

PURPOSE: To test the hypothesis that the retinamide N-(4-hydroxyphenyl)retinamide (fenretinide) would be clinically active potentially via receptor-independent apoptosis and receptor-dependent effects in natural retinoid-resistant oral leukoplakia patients--the first test of this hypothesis in any in vivo setting. EXPERIMENTAL DESIGN: A phase II trial of fenretinide (200 mg/d for 3 months) in oral leukoplakia patients who had not responded (de novo resistance) or who had responded and then relapsed (acquired resistance) to previous treatment with natural retinoids. We analyzed apoptosis via the terminal deoxynucleotidyl transferase-mediated nick end labeling in situ DNA fragmentation assay. RESULTS: We accrued 35 evaluable patients with retinoid-resistant oral leukoplakia, 12 (34.3%) had partial responses to fenretinide (95% confidence interval, 19.2-52.4%), and response was associated with acquired resistance to natural retinoids (P = 0.015, Fisher's exact test). Nine responders progressed within 9 months of stopping fenretinide. Toxicity was minimal and compliance was excellent. Mean apoptosis values (SE) increased from 0.35% (0.25%) at baseline to 1.18% (0.64%) at 3 months (P = 0.001, sign test); this increase did not correlate with clinical response. The increases in 3-month mean serum concentrations of fenretinide (0.23 micromol/L) and N-(4-methoxyphenyl)retinamide (0.57 micromol/L) correlated with decreased retinol concentrations [Spearman correlation coefficient of -0.57 (P = 0.001) and -0.43 (P = 0.01), respectively]. CONCLUSIONS: Low-dose fenretinide was clinically active and produced a small increase in apoptosis in retinoid-resistant oral leukoplakia.

PMID: 16707609 [PubMed - indexed for MEDLINE]

(A3) HIV Phenotypes, oral lesions, and management of HIV-related disease.

Adv Dent Res. 2006;19(1):122-9

Authors: Blignaut E, Patton LL, Nittayananta W, Ramirez-Amador V, Ranganathan K, Chattopadhyay A

Workshop participants discussed: the role of HIV subtypes in disease; the treatment of oral candidiasis; the relationship between and among viral load, CD4+ counts, oral candidiasis and oral hairy leukoplakia, pigmentation; and the development of a reliable oral index to predict disease progression. Regarding HIV, the literature revealed that Type I (HIV-I), in particular group M, is involved in the majority (90%) of documented infections, and groups N and O to a lesser extent. Viral envelope diversity led to the subclassification of the virus into nine subtypes, or clades-A-D, F-H, J, and K-each dominating in different geographical areas. HIV-2, currently occurring mostly in West Africa, appears to be less virulent. No evidence could be produced of any direct impact of type, subtype, or clade on oral lesions, and participants believed that further research is not feasible. Oral candidiasis in patients from resource-poor countries should be prevented. When the condition does occur, it should be treated until all clinical symptoms disappear. Oral rinsing with an antimicrobial agent was suggested to prevent recurrence of the condition, to reduce cost, and to prevent the development of antifungal resistance. Lawsone methyl ether, isolated from a plant (Rhinacanthus nasutus leaves) in Thailand, is a cost-effective mouthrinse with potent antifungal activity. Evidence from a carefully designed prospective longitudinal study on a Mexican cohort of HIV/AIDS patients, not receiving anti-retroviral treatment, revealed that the onset of oral candidiasis and oral hairy leukoplakia was heralded by a sustained reduction of CD4+, with an associated sharp increase in viral load. Analysis of the data obtained from a large cohort of HIV/AIDS patients in India could not establish a systemic or local cause of oral melanin pigmentation. A possible explanation was a dysfunctional immune system that increased melanin production. However, longitudinal studies may contribute to a better understanding of this phenomenon. Finally, a development plan was presented that could provide a reliable prediction of disease progression. To be useful in developing countries, the index should be independent of costly blood counts and viral load.

PMID: 16672562 [PubMed - indexed for MEDLINE]

Oral lesions in HIV infection in developing countries: an overview.

Adv Dent Res. 2006;19(1):63-8

Authors: Ranganathan K, Hemalatha R

HIV infection is a major global health problem affecting developing and developed countries alike. Oral lesions that are associated with this disease are important, since they affect the quality of life of the patient and are useful markers of disease progression and immunosuppression. Oral lesions in HIV infection have been well-documented in developed countries, but there are fewer reports on oral lesions from developing countries. Oral candidiasis is the most common opportunistic infection seen in all continents. Kaposi's sarcoma has been reported only from Africa and Latin America, while histoplasmosis and penicilliosis were reported in patients with advanced disease from Thailand. HIV-associated salivary gland disease has a high prevalence in Africa and Latin America, especially in the pediatric group. It is clear that there are considerable regional variations in the oral manifestations of HIV infection, depending both on the populations studied and on the clinical expertise available, among other factors. Well-designed and -documented studies are necessary for the correct assessment of the nature and magnitude of the problem in developing countries, if oral health measures are to be effectively formulated for the HIV-infected.

PMID: 16672552 [PubMed - indexed for MEDLINE]

Prospective study of alcohol consumption and risk of oral premalignant lesions in men.

Cancer Epidemiol Biomarkers Prev. 2006 Apr;15(4):774-81

Authors: Maserejian NN, Joshipura KJ, Rosner BA, Giovannucci E, Zavras AI

Recent case-control studies indicate that alcohol increases the risk of oral premalignant lesions (OPL) among tobacco users, but the independent association between alcohol and OPL remains unclear. We prospectively evaluated the association between alcohol consumption and the incidence of OPL. Participants were 41,458 men in the Health Professionals Follow-up Study. Alcohol consumption was assessed every 4 years using validated food frequency questionnaires. We confirmed clinically or histopathologically diagnosed OPL events occurring between 1986 and 2002 by medical record review (193 cases). Multivariate-adjusted relative risks of OPL were calculated from Cox proportional hazards models. With detailed control for tobacco and other variables, multivariate relative risks (95% confidence intervals) were 1.7 (0.9-3.2) for drinkers of 0.1 to 14.9 g/d, 2.9 (1.5-5.6) for 15 to 29.9 g/d, and 2.5 (1.3-5.1) for > or =30 g/d, compared with nondrinkers. Approximately one additional drink per day (12.5 g) was associated with a 22% increase in risk (P < 0.001). The associations did not vary by beverage type, frequency, or consumption with meals. Results were similar when restricted to cases of oral epithelial dysplasia. Alcohol increased OPL risk in never-users of tobacco as well as in past or current users. An interaction between alcohol and tobacco was apparent by their more-than-additive joint effects. Alcohol is an independent risk factor for OPL, regardless of beverage type or drinking pattern. Recommendations to reduce alcohol intake have the potential to reduce incidence of OPL in nonsmokers and smokers alike.

PMID: 16614123 [PubMed - indexed for MEDLINE]

[Expression of survivin and its correlation to angiogenesis in oral squamous cell carcinoma]

Ai Zheng. 2005 Nov;24(11):1354-7

Authors: Liu YM, Huang JH, Feng DY, Guo XC

BACKGROUND & OBJECTIVE: Survivin can block the cell apoptosis through inhibiting the functions of Caspase-3 and Caspase-7, and selectively overexpresses in common human cancers. This study was designed to investigate the effects of Survivin on tumorigenesis and development of oral cancer and its correlation to angiogenesis. METHODS: The expression of Survivin in 8 specimens of normal oral mucosa, 14 specimens of dysplastic leukoplakia and 47 specimens of oral squamous cell carcinoma (OSCC), and the expression of CD34 in the 47 specimens of OSCC was detected by SP immunohistochemistry. Microvessel density (MVD) was also assessed. The correlations of Survivin expression to MVD and clinicopathologic features of the OSCC patients were analyzed. RESULT: The positive rates of Survivin were 0% in normal oral mucosa, 14.24% in dysplastic leukoplakia, and 55.32% in OSCC. Survivin expression was significantly stronger in OSCC than in normal oral mucosa and dysplastic leukoplakia (P < 0.05), while there was no difference between the last 2 groups (P > 0.05). Survivin expression was significantly stronger in moderately and poorly differentiated OSCC than in well differentiated OSCC (P < 0.05); the positive rate of Survivin was significantly higher in OSCC with lymph node metastasis than in OSCC without lymph node metastasis(71.43% vs. 38.89%, P < 0.05). In OSCC, MVD was increased (25.87 +/- 12.10, 28.70 +/- 7.69, 35.42 +/- 10.09, 41.13 +/- 9.62, respectively) along with the strengthened Survivin expression (-, +, 2+, 3+) (P < 0.05). CONCLUSION: Survivin expression is up-regulated in OSCC, and closely related with tumor cell differentiation, lymph node metastasis, and MVD; it may play an important role in tumorigenesis and development of OSCC.

PMID: 16552962 [PubMed - indexed for MEDLINE]

DNA cytometry of oral leukoplakia and oral lichen planus.

Med Oral Patol Oral Cir Bucal. 2006 Mar;11(2):E221; author reply E221-2

Authors: Martin P

PMID: 16505806 [PubMed - indexed for MEDLINE]

E-cadherin, laminin and collagen IV expression in the evolution from dysplasia to oral squamous cell carcinoma.

Med Oral Patol Oral Cir Bucal. 2006 Mar;11(2):E100-5

Authors: Santos-Garc&#xED;a A, Abad-Hernández MM, Fonseca-Sánchez E, Julián-González R, Galindo-Villardón P, Cruz-Hernández JJ, Bullón-Sopelana A

OBJECTIVES: Study the loss or reduction of the cellular adhesion mediated for E-cadherin in oral leukoplakias, oral squamous cell carcinomas and metastatic nodules. Study the loss of continuity of the laminin and collagen IV expression in the epithelial basal membrane from the biological development of the oral leukoplakias and oral carcinomas. MATERIAL AND METHOD: we have studied 124 samples of patient pays leukoplakias and oral carcinomas with diverse diagnosis that embrace from normal epithelium (13 samples), mild dysplasias (2), moderate dysplasias (12), in situ carcinomas (13), microinvasive carcinomas (11) oral squamous cell carcinomas (64 samples) and metastatic nodules (9). 7 blocks of tissue microarrays were built with needle of 2mm and was carried out a study by means of immunohistochemical technique for E-cadherin (clone 36, Biogenex), Laminin (078P, Biogenex) and Collagen IV (PHM12, Biogenex). RESULTS: In Mild and Moderate Dysplasias the results present loss of E-cadherin, Laminin, and Collagen IV (20%) expression. in situ and microinvasive carcinomas, the results presented loss of E-cadherin expression (73%), and loss in Laminin and Collagen IV expression (57%). In the squamous cell carcinomas , we find E-cadherin underexpression (90%) and discontinuity in the Basal Membrane. (70%). All the metastatic nodules presented loss of E-cadherin expression and discontinuity in Laminin and Collagen IV expression. CONCLUSIONS: The loss of E-cadherin expression is increased when increasing the dysplasia grade of lesions. The loss of continuity in the laminin and Collagen IV expression follow a parallel evolution from dysplasias to metastatic nodules. The underexpression of the three markers has been significant in the evolution of the oral lesions.

PMID: 16505783 [PubMed - indexed for MEDLINE]

Epstein-Barr virus in oral hairy leukoplakia scrapes: identification by PCR.

Braz Oral Res. 2005 Oct-Dec;19(4):317-21

Authors: Komatsu TL, Rivero ER, Gallottini de Magalhães MH, Nunes FD

Oral hairy leukoplakia (OHL) is a lesion associated with a compromised immune system, and its diagnosis is determined by the demonstration of the presence of Epstein-Barr virus (EBV) in lesional tissue. The purpose of this article was to develop a simple technique to help the diagnosis of OHL, using PCR as an alternative technique to evidence EBV in scrapings. DNA samples were obtained by scraping the lateral border of the tongue of 38 adult patients: 29 HIV-positive patients (4 with clinical evidence of OHL; 4 with history of OHL, but without lesion at the moment the samples were collected; and 21 without clinical evidence of OHL), and 9 healthy volunteers for the control group. DNA was extracted from scrapes and amplified by PCR using specific primers for EBV. Of the 29 cases of HIV-positive patients, 22 (75.86%) were positive for EBV: 2 patients with clinical evidence of OHL, 4 patients with history of OHL, but without lesion at the moment the samples were collected, and 16 patients without clinical evidence of OHL. In the control group, samples of 5 (55.56%) healthy volunteers presented amplification for EBV. We concluded that the use of PCR in oral scrapes suggests a high sensitivity but low specificity for the diagnosis of OHL.

PMID: 16491263 [PubMed - indexed for MEDLINE]

[Expression and clinical significance of VEGF-C and Flt-4 in tongue squamous cell carcinoma]

Ai Zheng. 2006 Feb;25(2):235-40

Authors: Li QL, Chen FJ, Zeng ZY, Yang AK, Wu QL, Zhang HZ, Hou JH

BACKGROUND & OBJECTIVE: Vascular endothelial growth factor-C (VEGF-C) could induce lymphangiogenesis in or around solid tumor, and is closely related with lymphatic metastasis. This study was to investigate the expression and clinical significance of VEGF-C and its receptor fms-like tyrosine kinase-4 (Flt-4) in tongue squamous cell carcinoma (TSCC). METHODS: The expression of VEGF-C and Flt-4 in 99 specimens of TSCC and 17 specimens of benign tongue epithelial lesions was detected by LSAB immunohistochemistry. The correlations of expression of VEGF-C and Flt-4 to the clinicopathologic features and prognosis of TSCC were analyzed. RESULTS: The positive rates of VEGF-C and Flt-4 were significantly higher in TSCC than in benign tongue epithelial lesion (35.35% vs. 5.88%, and 40.40% vs. 5.88%, P<0.05). The positive rate of VEGF-C was significantly higher in TSCC with cervical lymph node metastasis than in TSCC without metastasis (43.75% vs. 20%, P<0.05), and significantly lower in stage I-II TSCC than in stage III-IV TSCC (18.52% vs. 41.67%, P<0.05). The cumulative 5-year survival rates of the patients with positive expression of either VEGF-C or Flt-4 were significantly lower than those of the patients with negative expression of either VEGF-C or Flt-4 (45.08% vs. 68.25%, and 38.03% vs. 75.46%, P<0.05). CONCLUSIONS: The positive rates of VEGF-C and Flt-4 are significantly higher in TSCC than in benign tongue epithelial lesions. The expression of VEGF-C is correlated with cervical lymph node metastasis and clinical stage. The prognosis of TSCC patients with high expression of VEGF-C and Flt-4 is poor.

PMID: 16480594 [PubMed - indexed for MEDLINE]

Kindler syndrome.

Indian J Dermatol Venereol Leprol. 2005 Sep-Oct;71(5):348-50

Authors: Kaviarasan PK, Prasad PV, Shradda , Viswanathan P

Kindler syndrome is a rare autosomal recessive disorder associated with skin fragility. It is characterized by blistering in infancy, photosensitivity and progressive poikiloderma. The syndrome involves the skin and mucous membrane with radiological changes. The genetic defect has been identified on the short arm of chromosome 20. This report describes an 18-year-old patient with classical features like blistering and photosensitivity in childhood and the subsequent development of poikiloderma. The differential diagnosis of Kindler syndrome includes diseases like Bloom syndrome, Cockayne syndrome, dyskeratosis congenita, epidermolysis bullosa, Rothmund-Thomson syndrome and xeroderma pigmentosum. Our patient had classical cutaneous features of Kindler syndrome with phimosis as a complication.

PMID: 16394462 [PubMed - indexed for MEDLINE]

Epidemiological and clinicopathological study of oral leukoplakia.

Indian J Dermatol Venereol Leprol. 2005 May-Jun;71(3):161-5

Authors: Mishra M, Mohanty J, Sengupta S, Tripathy S

BACKGROUND: Oral white lesions that cannot be clinically or pathologically characterized by any specific disease are referred to as leukoplakia. Such lesions are well known for their propensity for malignant transformation to the extent of 10-20%.Exfoliative cytology is a simple and useful screening tool for detection of malignant or dysplastic changes in such lesions. AIMS: A clinico-epidemiological and cytological study of oral leukoplakia was undertaken to detect their malignant potential and value of cytology in diagnosis. METHODS: This 2 year duration multicentre study was undertaken on all patients presenting with oral white lesions to the out patient department of the two institutions. Those cases in which a specific cause (infective, systemic disease or specific disease entity) for the white lesions were elicited were excluded from the study. The group with idiopathic white lesions was included in the study and was subjected to periodic exfoliative cytological study at three monthly intervals to detect any malignant change. Patients presenting less than two times for follow up were excluded from the final analysis of the study. RESULTS: Out of total 2920 patients studied, 89.53% showed benign, 9.93% showed dysplastic and, 0.72% showed malignant cells on exfoliative cytological study. All the dysplastic and malignant lesions were subjected to histopathological study by incisional biopsy. Among the dysplastic lesions 13.79% proved benign and the rest true dysplastic. Among the cytologically malignant group 4.76% showed dysplasia and the rest true malignant lesions. CONCLUSION: Persistent leukoplakia has a potential for malignant transformation and exfoliative cytology could be a simple method for early detection of dysplastic and malignant changes.

PMID: 16394403 [PubMed - indexed for MEDLINE]

Prevalence of oral lesions in HIV patients related to CD4 cell count and viral load in a Venezuelan population.

Med Oral Patol Oral Cir Bucal. 2006 Jan;11(1):E33-9

Authors: Bravo IM, Correnti M, Escalona L, Perrone M, Brito A, Tovar V, Rivera H

AIM: To determine the prevalence of oral lesions in a HIV+ group of patients, related to CD4 cell count and viral load in a Venezuelan population. MATERIALS AND METHODS: In the present study, we evaluated 75 HIV+ adult patients, attended at the Center of Infectious Diseases, at the Faculty of Dentistry, Central University of Venezuela. Each patient was clinically examined for detection of oral mucosal lesions. In addition, CD4 cell count was determined by flow cytometry, as well as viral load by RT-PCR (Amplicor HIV-RNA, TM test 1.5, Roche). RESULTS: 85% (64/75) of HIV/AIDS patients showed associated HIV lesions. Oral Candidiasis constituted the most common lesion representing a 61% (39/64), followed by Oral Hairy Leukoplakia 53% (34/64); Oral Leukoplakia 34% (22/64), Melanic Hyperpigmentation 38% (18/64); Papilloma 13 (6/64), Lineal Gingival Erythema 8% (5/64); Aphtous Recurrent Stomatitis 5% (4/64) and Kaposi's Sarcoma 5% (3/64). Only one case of the following lesions were represented by Non Hodgkin Lymphoma, Multifocal Epithelial Hyperplasia, Recurrent Herpes, Histoplasmosis and Molluscum Contagiosum. The patients with a viral load of 30.000 copies/mm3 exhibited oral lesions related with HIV, independent of CD4 cell count, although patients with CD4+ levels of 200 cel/mm3 were more susceptible to develop these lesions. CONCLUSIONS: The most common oral lesion was Oral Candidiasis followed by Oral Hairy Leukoplakia, Oral Leukoplakia and Melanic Hyperpigmentation. A high viral load was strongly associated to the oral lesions occurrence independently of CD4+ cell count.

PMID: 16388291 [PubMed - indexed for MEDLINE]

Oral manifestations of HIV disease.

Top HIV Med. 2005 Dec-2006 Jan;13(5):143-8

Authors: Reznik DA

HIV-related oral conditions occur in a large proportion of patients, and frequently are misdiagnosed or inadequately treated. Dental expertise is necessary for appropriate management of oral manifestations of HIV infection or AIDS, but many patients do not receive adequate dental care. Common or notable HIV-related oral conditions include xerostomia, candidiasis, oral hairy leukoplakia, periodontal diseases such as linear gingival erythema and necrotizing ulcerative periodontitis, Kaposi's sarcoma, human papilloma virus-associated warts, and ulcerative conditions including herpes simplex virus lesions, recurrent aphthous ulcers, and neutropenic ulcers.

PMID: 16377852 [PubMed - indexed for MEDLINE]

Squamous cell carcinoma of the oral tissues: a comprehensive review for oral healthcare providers.

J Contemp Dent Pract. 2005 Nov 15;6(4):1-16

Authors: Bsoul SA, Huber MA, Terezhalmy GT

North Americans in 2004 were projected to die from oral and pharyngeal cancer at a rate of 1.2 per hour. Oral healthcare providers can be instrumental in reducing the incidence of oral and pharyngeal premalignant and malignant lesions by identifying patients with high-risk behavior, educating their patients about the consequences of their high-risk behavior, and by early detection of premalignant and malignant conditions. The fact only 34% of the cancers of the oral cavity and larynx are localized at the time of diagnosis and evidence that at least one third of the patients diagnosed with an oral or pharyngeal malignancy have undergone oral cancer screening within the past three years suggests the current protocol for the early detection of pre-malignant or malignant changes appears to be deficient. To facilitate early diagnosis, oral healthcare providers must take into consideration the capriciousness of oral cancer and must be familiar with the availability and application of diagnostic modalities beyond conventional visual inspection and palpation of oral soft tissues. This article provides a comprehensive review of the disease for healthcare professionals.

PMID: 16299602 [PubMed - indexed for MEDLINE]

Areca (betel) nut chewing habit among high-school children in the Commonwealth of the Northern Mariana Islands (Micronesia).

Bull World Health Organ. 2005 Sep;83(9):656-60

Authors: Oakley E, Demaine L, Warnakulasuriya S

OBJECTIVE: To investigate the prevalence of its use by high-school children in Saipan in Micronesia. Usage of the areca nut is indigenous to south Asia and the western and south Pacific. Some serious health effects of areca nut chewing are recognized and the International Agency for Research on Cancer has recently classified regular use of areca nut as being carcinogenic to humans. Information on usage by young people, however, is scarce. METHODS: Data on consumption of areca nut were obtained by a self-administered questionnaire. Following an oral mucosal examination using WHO criteria any detectable oral mucosal diseases were recorded. FINDINGS: Of 309 schoolchildren surveyed (mean age 16.3 +/- 1.5 years), 63.4% claimed regular use, the highest level recorded in any school population survey. Significant oral diseases detected were oral leukoplakia in 13% and oral submucous fibrosis in 8.8% of children. CONCLUSION: These findings from Saipan suggest that areca nut chewing starts at a young age in Micronesia. As many users develop dependency this raises important concerns regarding its consequences for oral health.

PMID: 16211156 [PubMed - indexed for MEDLINE]

Increased risk of oral leukoplakia and cancer among mixed tobacco users carrying XRCC1 variant haplotypes and cancer among smokers carrying two risk genotypes: one on each of two loci, GSTM3 and XRCC1 (Codon 280).

Cancer Epidemiol Biomarkers Prev. 2005 Sep;14(9):2106-12

Authors: Majumder M, Sikdar N, Paul RR, Roy B

An individual's susceptibility to oral precancer and cancer depends not only on tobacco exposure but also on the genotypes/haplotypes at susceptible loci. In this hospital-based case-control study, 310 cancer patients, 197 leukoplakia patients, and 348 controls were studied to determine risk of the disease due to polymorphisms at three sites on XRCC1 and one site on XRCC3. Independently, variant genotypes on these loci did not modulate risk of leukoplakia and cancer except for the XRCC1 (codon 280) risk genotype in exclusive smokeless tobacco users with leukoplakia [odds ratios (OR), 2.4; 95% confidence intervals (CI), 1.0-5.7]. But variant haplotypes, containing one variant allele, on XRCC1 increased the risk of leukoplakia (OR, 1.3; 95% CI, 1.0-1.7). Among stratified samples, mixed tobacco users, carrying variant haplotypes, also had increased risk of both leukoplakia (OR, 2.2; 95% CI, 1.3-3.9) and cancer (OR, 1.9; 95% CI, 1.2-3.1). In a previous study on this population, it was shown that the GSTM3 (A/A) genotype increased the risk of oral leukoplakia and cancer among smokers, which has also been substantiated in this study with expanded sample sizes. The simultaneous presence of two risk genotypes in smokers, one on each of two loci, GSTM3 and XRCC1 (codon 280), increased the risk of cancer (OR, 2.4; 95% CI, 1.0-5.8). Again, smokers carrying two risk genotypes, one on each of two loci, GSTM3 and XRCC1 (codon 399), were also overrepresented in both leukoplakia and cancer populations (P(trend) = 0.02 and 0.04, respectively) but enhancement of risks were not observed; probably due to small sample sizes. Therefore, the presence of variant haplotypes on XRCC1 and two risk genotypes, one on each of two loci, GSTM3 and XRCC1, could be useful to determine the leukoplakias that might progress to cancer in a group of patients.

PMID: 16172217 [PubMed - indexed for MEDLINE]

Tobacco cessation for the dental team: a practical guide part I: background & overview.

J Contemp Dent Pract. 2005 Aug 15;6(3):158-66

Authors: Davis JM

Dental professionals are strategically placed to be the leaders in tobacco prevention and cessation as they provide preventive and therapeutic services to a basically healthy population on a regular basis. By expanding the dental exam, diagnosis, and treatment to include tobacco cessation, a potentially life saving element of care is added to an established service. In addition periodontal disease and the potential for oral cancer mandate the inclusion of tobacco cessation services into dental care. Though dental professionals are aware of the health issues associated with tobacco use, they often feel ill prepared or uncomfortable presenting patients with a clear cessation message. In this, the first of a two-part article, the purpose is to provide dental professionals with the foundational knowledge necessary to provide effective tobacco cessation as a normal part of patient care.

PMID: 16127485 [PubMed - indexed for MEDLINE]

A noninvasive genetic screening test to detect oral preneoplastic lesions.

Lab Invest. 2005 Dec;85(12):1481-8

Authors: Bremmer JF, Braakhuis BJ, Ruijter-Schippers HJ, Brink A, Duarte HM, Kuik DJ, Bloemena E, Leemans CR, van der Waal I, Brakenhoff RH

Early diagnosis of oral squamous cell carcinoma (OSCC) may have a major impact on survival and quality of life. Recent studies have shown that the majority of OSCC is preceded by precursor lesions characterized by genetic alterations. The aim of this study was to develop and evaluate a noninvasive screening test for oral preneoplastic lesions, based on genetic alterations as marker. Various methods to obtain a high yield of cells by brushing a small area of the oral mucosa were compared. A novel genetic assay, multiplex ligation-dependent probe amplification (MLPA), was applied that enables the measurement of gains and losses at 40 different chromosomal locations in one PCR reaction using 150 ng DNA. MLPA was performed on DNA of normal and dysplastic oral mucosa as well as of OSCC with the intention to select a specific probe set for accurate detection of precursor lesions in the oral cavity. The assay was correlated to loss of heterozygosity analysis using microsatellite markers, and evaluated on noncancer subjects and patients with oral leukoplakia. A noninvasive sampling method was developed with DNA yields ranging from 150 to 600 ng. Using 120 probes, we could detect large differences with MLPA in the number of alterations between normal vs dysplastic and dysplastic vs tumor tissue with P-values <0.001. A significant correlation was found between the number of alterations as detected by MLPA and the analysis for allelic loss. The available data enabled the selection of a set of 42 MLPA probes, which had the power to optimally discriminate between normal and dysplastic tissue. Our data show that MLPA is a sensitive, reliable, high-throughput and easy-to-perform technique, enabling the detection of genetic alterations on small noninvasive samples and can be considered a promising method for population-based screening of preneoplastic lesions in the oral cavity.

PMID: 16127456 [PubMed - indexed for MEDLINE]

Assessment of c-Jun, c-Fos and cyclin D1 in premalignant and malignant oral lesions.

J Oral Sci. 2005 Jun;47(2):71-6

Authors: Turatti E, da Costa Neves A, de Magalh&#xE3;es MH, de Sousa SO

Some oral cancers are known to develop from dysplastic oral epithelium. In the present study, the expression of c-Jun, c-Fos, and cyclin D1 proteins in oral epithelial lesions with different degrees of dysplasia, and in oral squamous cell carcinomas (OSCCs) was evaluated. Eighteen cases of mild dysplasia, 23 cases of moderate to severe dysplasia and 24 OSCCs were studied immunohistochemically. Additionally, 15 sections of oral mucosa without any evidence of dysplasia were included in the study. Results: c-Jun expression increased according to the degree of oral dysplasia, with the greatest expression found in OSCC. c-Fos expression was intense in normal mucosa, reduced in mild dysplasia and high in moderate to severe dysplasia and in OSCCs. Cyclin D1 was expressed in only a few cases of moderate to severe dysplasia and in most of the OSCCs. Statistical analysis showed a correlation between the three proteins and the degree of epithelial alteration. The present results indicate a possible role of c-Jun and c-Fos in malignant transformation of oral mucosa.

PMID: 16050486 [PubMed - indexed for MEDLINE]

Interferon regulatory factor 7 is negatively regulated by the Epstein-Barr virus immediate-early gene, BZLF-1.

J Virol. 2005 Aug;79(15):10040-52

Authors: Hahn AM, Huye LE, Ning S, Webster-Cyriaque J, Pagano JS

Virus infection stimulates potent antiviral responses; specifically, Epstein-Barr virus (EBV) infection induces and activates interferon regulatory factor 7 (IRF-7), which is essential for production of alpha/beta interferons (IFN-alpha/beta) and upregulates expression of Tap-2. Here we present evidence that during cytolytic viral replication the immediate-early EBV protein BZLF-1 counteracts effects of IRF-7 that are central to host antiviral responses. We initiated these studies by examining IRF-7 protein expression in vivo in lesions of hairy leukoplakia (HLP) in which there is abundant EBV replication but the expected inflammatory infiltrate is absent. This absence might predict that factors involved in the antiviral response are absent or inactive. First, we detected significant levels of IRF-7 in the nucleus, as well as in the cytoplasm, of cells in HLP lesions. IRF-7 activity in cell lines during cytolytic viral replication was examined by assay of the IRF-7-responsive promoters, IFN-alpha4, IFN-beta, and Tap-2, as well as of an IFN-stimulated response element (ISRE)-containing reporter construct. These reporter constructs showed consistent reduction of activity during lytic replication. Both endogenous and transiently expressed IRF-7 and EBV BZLF-1 proteins physically associate in cell culture, although BZLF-1 had no effect on the nuclear localization of IRF-7. However, IRF-7-dependent activity of the IFN-alpha4, IFN-beta, and Tap-2 promoters, as well as an ISRE promoter construct, was inhibited by BZLF-1. This inhibition occurred in the absence of other EBV proteins and was independent of IFN signaling. Expression of BZLF-1 also inhibited activation of IRF-7 by double-stranded RNA, as well as the activity of a constitutively active mutant form of IRF-7. Negative regulation of IRF-7 by BZLF-1 required the activation domain but not the DNA-binding domain of BZLF-1. Thus, EBV may subvert cellular antiviral responses and immune detection by blocking the activation of IFN-alpha4, IFN-beta, and Tap-2 by IRF-7 through the medium of BZLF-1 as a negative regulator.

PMID: 16014964 [PubMed - indexed for MEDLINE]

Valuation of exfoliative cytology as prediction factor in oral mucosa lesions.

Med Oral Patol Oral Cir Bucal. 2005;10 Suppl 2:E92-102

Authors: Brunotto M, Z&#xE1;rate AM, Cismondi A, Fernández Mdel C, Noher de Halac RI

The aim of this study was immunolabeling oncoproteins Ck14, p53, p21 and Bcl-2 in order to evaluate their expression in premalignant and malignant stomatological lesions in oral epithelial, and to compare this expression with exfoliative cytology alterations in the same patients. It was studied biopsies and cytologies of 13 subjects with oral lichen planus, with or without Human Papilloma Virus (HPV), leukoplakia and squamous cell carcinoma clinically diagnosed and confirmed by anatomopathological studies. The oral lichen planus lesion presented binuclei orange cells; and in leukoplakia lesions only orange stained was observed; meanwhile koilocytes, inflammatory cells, enlarge nuclear volume and pathogenic microorganisms were observed in the HPV infections and squamous cells carcinoma (SCC). The Ck14, p53, p21 and Bcl-2 proteins were found modified in the leukoplakia, oral lichen planus and cancer. Cytological alterations and positive immunolabeling or over-expression of Ck14 cytokeratine in the upper epithelial stratus should be indicator of malignant transformations as doing subsequence exams.

PMID: 15995578 [PubMed - indexed for MEDLINE]

Novel management of oral cancer: a paradigm of predictive oncology.

Clin Med Res. 2004 Nov;2(4):233-42

Authors: Sudbø J

The rationale for molecular-targeted prevention of oral cancer is strong. Oral cancer is a major global threat to public health with 300,000 new cases diagnosed worldwide on an annual basis. Notably, the great morbidity and mortality rates of this devastating disease have not improved in decades. Oral cancer development is a tobacco-related multistep and multifocal process involving field carcinogenesis and intraepithelial clonal spread. Biomarkers of genomic instability, such as aneuploidy and allelic imbalance, can accurately measure the cancer risk of oral premalignant lesions or intraepithelial neoplasia (IEN). Retinoid-oral IEN studies (e.g., retinoid acid receptor-beta, p53, genetic instability, loss of heterozygosity, and cyclin D1) have advanced the overall understanding of the biology of intraepithelial carcinogenesis and preventive agent molecular mechanisms and targets, important advances for monitoring preventive interventions, assessing cancer risk, and pharmacogenomics. Clinical management of oral IEN varies from watchful waiting to complete resection, although complete resection does not prevent oral cancer in high-risk patients. New approaches, such as interventions with molecular-targeted agents and agent combinations in molecularly defined high-risk oral IEN patients, are urgently needed to reduce the devastating worldwide consequences of oral cancer.

PMID: 15931363 [PubMed - indexed for MEDLINE]

[The expressions of cyclooxygenase-2 (Cox-2),VEGF in oral squamous cell carcinoma and precancerous lesions and their significances]

Shanghai Kou Qiang Yi Xue. 2005 Apr;14(2):173-6

Authors: Sun XJ, Ma J, Zhang H, Wang XK, Li JH

PURPOSE: To determine expression of Cox-2 in oral squamous cell carcinoma (SCC) and oral leukoplakia and the relation to VEGF. METHODS: Immunohistochemical staining was used to quantify Cox-2 and VEGF expressions in specimens from 48 patients with oral SCC (including 20 well differentiated cases, 16 moderately differentiated cases and 12 low differentiated cases), 35 patients with oral leukoplakia (epithelial dysplasia), and 20 patients with normal oral mucosa. All specimens were analyzed by conformation quantitative assay system, their stain-strength was calculated. Statistical analysis of ANOVA and linear correlation was performed using SAS statistical software. RESULTS: The expressions of Cox-2 and VEGF increased significantly as the progression of oral mucosa from normal to oral leukoplakia and oral SCC. The expression of Cox-2 reached peak in well differentiated SCC (0.167+/-0.004), and its expression decreased sharply as differentiation became poor. On the other hand, the expression of VEGF reached peak in well differentiated carcinoma (0.143+/-0.014). The expressions of Cox-2 and VEGF had negative correlation in differently differentiated SCC tissues (r=0.649, P<0.001). CONCLUSION: The expressions of Cox-2 and VEGF were significantly up-regulated in the early carcinogenesis of oral mucosa, and they may be influenced each other. Thus, they were important in the carcinogenesis and progression of oral SCC.

PMID: 15886845 [PubMed - in process]

Oral lesions in a group of kidney transplant patients.

Med Oral Patol Oral Cir Bucal. 2005 May-Jul;10(3):196-204

Authors: de la Rosa-Garc&#xED;a E, Mondragón-Padilla A, Irigoyen-Camacho ME, Bustamante-Ramírez MA

AIM: To assess the prevalence of oral mucosa lesions (OL) in a group of kidney transplant (KT) patients, and analyze possible OL associations with one another and with drugs use and relevant clinical and laboratory variables. METHODOLOGY: Transversal study, in which consecutive KT patients from the nephrology outpatient service at a General Zonal Hospital were examined. The prevalence of several types of OL was assessed, and their possible statistical associations with one another and total leukocyte count, renal function, the simplified oral hygiene index (S-OHI), cyclosporin-A (CsA) dose and blood levels, and nifedipine use was analyzed. A logistic regression model was used to analyze the association between gingival hyperplasia (GH) and CsA dose and nifedipine use. RESULTS: Fifty (55.6%) men and forty (44.4%) women were studied. Sixty percent of the patients had at least one OL. Oral candidiasis (OC) was found in 18.7%; 13% had lesions clinically compatible with hairy leukoplakia (CHL). An association was found between OC and CHL (P<0.05). Saburral tongue (ST) was found in 22% of the patients and gingival hyperplasia (GH) in 49%, which was distributed as follows: Grade 1 in 11 (12.2%); Grade 2 in 26 (28.9%), and Grade 3 in 7 (7.8%). Logistic regression results showed an association between GH and poor oral hygiene (P< 0.001), but not to either CsA dose or blood levels, or nifedipine use (P=0.075). CONCLUSION: Sixty percent of the KT patients had at least one OL. The association between GH and poor oral hygiene corroborate the need for oral hygiene practices supervision in the transplant patient.

PMID: 15876960 [PubMed - indexed for MEDLINE]

DNA cytometry of oral leukoplakia and oral lichen planus.

Med Oral Patol Oral Cir Bucal. 2005;10 Suppl 1:E9-14

Authors: Femiano F, Scully C

BACKGROUND: DNA cytometry is a technique that allows densitometric analysis of nuclear DNA of cells and in this way the evaluation of DNA ploidy. OBJECTIVE: The purpose of the present study was the evaluation of DNA ploidy in oral leukoplakia and oral lichen planus and correlation with histological dysplasia. METHODS: We analyzed oral incisional biopsies from a group of 40 patients with oral leukoplakias (20 homogeneous and 20 non-homogeneous) and 45 patients with oral lichen planus (25 erosive, 20 reticular), by DNA cytomorphometry, after conventional histological examination of sections stained with haematoxylin and eosin. RESULTS AND CONCLUSIONS: Eight of 20 non-homogeneous leukoplakias showed aneuploidy; (3 showed mild aneuploidy) and only 2 specimens of erosive lichen planus showed moderate aneuploidy, while all 20 cases of reticular lichen planus were diploid. There was not concordance between DNA ploidy and the degree of histological assessed dysplasia.

PMID: 15800471 [PubMed - indexed for MEDLINE]

Liquid-based preparations versus conventional cytology: specimen adequacy and diagnostic agreement in oral lesions.

Med Oral Patol Oral Cir Bucal. 2005 Mar-Apr;10(2):115-22

Authors: Hayama FH, Motta AC, Silva Ade P, Migliari DA

OBJECTIVE: To compare specimen adequacy and diagnostic agreement between liquid-based preparations and conventional smears in oral lesions, and to test the viability of immunocytochemical assay in liquid-based preparations from oral carcinoma lesions. MATERIAL AND METHODS: Samples were collected from 44 patients. Conventional smears were prepared first, using a cytobrush device. Then the brush, containing the residual material, was immersed in a preservative fluid. The sample in the preservative fluid was processed according to the manufacturer directions (AutoCyte, Inc. Elon College, North Carolina, USA). Slides of both techniques were stained by Papanicolaou method. For immunocytochemical assay, a cytokeratin pool AE1/AE3 (Dako, CA, USA) was applied in liquid-based preparations from oral carcinoma lesions following the Streptavidin-biotin-peroxidase method. Fisher's exact test was used; significance was set for P < or = 0.05. RESULTS: Both techniques agreed on cytologic diagnosis in every case they yielded an adequate specimen; in 3 cases conventional smear resulted in hypocellularity and therefore inadequate for analysis. On specimen analysis, the liquid-based cytology demonstrated a statistically significant, 41% overall improvement in smear thickness and 66% in cell distribution (P < or = 0.05), and a reduction in cell overlapping and presence of blood (P < or = 0.05). The cell morphology was better visualized in the liquid-based preparations. The immunocytochemical assay reactions were positive in all malignant cases, the visualization of the immunostained cells being especially clear. CONCLUSION: Both, the liquid-based preparation and conventional smear, are diagnostically reliable; the liquid-based method showed an overall improvement on sample preservation, specimen adequacy, visualization of cell morphology and reproducibility.

PMID: 15735543 [PubMed - indexed for MEDLINE]

Cyclooxygenase inhibitor ketorolac or mast cell stabilizers: immunologic challenges in cancer therapy.

Clin Cancer Res. 2005 Feb 1;11(3):1349-51; author reply 1351

Authors: Khatami M

PMID: 15709209 [PubMed - indexed for MEDLINE]

[Prognostic significance of cyclin D1, p27 and p63 expression in oral leukoplakia]

Magy Onkol. 2004;48(4):309-13

Authors: K&#xF6;vesi G, Szende B

Studies on the expression of genes regulating cell proliferation and apoptosis is of importance in relation to understanding the severity of the process and the possibility of malignant transformation. In the present study immunohistochemical demonstration of cyclin D1, p27 and p63 has been added to our previous investigations on Ki-67, p53 and apoptosis index. Clinical and pathological immunohistochemical studies on oral leukoplakias of 18 patients were performed. Clinically homogenous, non-homogenous or nodular, and erythroleukoplakia were distinguished. Pathologically the grading was made according to the degree of dysplasia. Immunoperoxidase reactions for cyclin D1, p27 and p63 were carried out, and the positivity was expressed in per cent, considering 1000 epithelial cells. Expression of cyclin D1 increased in parallel with the severity of leukoplakia. p27 expression was 14-16% in homogenous and nodular leukoplakias, whereas in erythroleukoplakia it decreased to 1-2%. p63 expression was 10% in average in homogenous, and 5% in nodular leukoplakias. While in erythroleukoplakias it increased to 20 per cent. The characteristic cyclin D1, p27 and p63 phenotype in various forms of leukoplakia may be considered as prognostic factors.

PMID: 15655576 [PubMed - indexed for MEDLINE]

Proteic expression of p53 and cellular proliferation in oral leukoplakias.

Med Oral Patol Oral Cir Bucal. 2005 Jan-Feb;10(1):5-8; 1-5

Authors: Santos-García A, Abad-Hernández MM, Fonseca-Sánchez E, Cruz-Hernández JJ, Bullón-Sopelana A

OBJECTIVES: We intend to know the protein expression of genetic alterations that take place in the early stages in the field cancerization of oral cavity in our means as well as to study the cellular proliferation by means of Ki-67 and the protein product expression of p53 to value if the alterations in the protein products expression of these markers happen in a sequential pathway through the different stages in the field cancerization of oral cavity. MATERIALS AND METHODS: A study was made by immunohistochemistry on 53 patients that presented lesions of oral leukoplaquia, assisted by the ENT service at University Hospital of Salamanca, from 1.990 up to 2000. 11 samples of normal epithelium, 15 mild to moderate dysplasias, 15 in situ carcinomas and 12 microinvasive carcinomas are included in the study. RESULTS: we find an increased cellular proliferation and p53 over-expression as we advance in the grade of severity histopathologic of these lesions. The most early alterations are a significant increase of cell proliferation in mild and moderate dysplasias and an increased p53 over-expression. CONCLUSIONS: Oral leukoplaquia is a precancerous stage that constitutes a cancerisable lesion due to the genetic alterations that mediate in the evolution of lesion. Routine Immunohistochemical and molecular study of these lesions allow us to know the protein expression of genetic alterations that can help in the early diagnosis and treatment of this pathology, having special relevance the study of Ki-67 in early stages and p53 in advanced lesions.

PMID: 15627901 [PubMed - indexed for MEDLINE]

[The expression of apoptosis-associated proteins Bcl-2, Bax in oral leukoplakia and lichen planus]

Shanghai Kou Qiang Yi Xue. 2004 Dec;13(6):497-501

Authors: Fan Y, Zhan Z, Peng T, Song XL, Feng ZQ

PURPOSE: The purpose of this study was to explore the pathogenesis and carcinogenesis of oral leukoplakia (LK) and oral lichen planus (OLP) by examining the expression of apoptosis-associated proteins Bcl-2 Bax in LK and OLP. METHODS: The expression of Bcl-2 and Bax were measured in 10 cases of normal oral mucosa,18 cases of OLP, 23 cases of LK and 22 cases of oral squamous cell carcinoma (SCC) by immunohistochemical assays. RESULTS: In the epithelial cell layer of LK and OLP, the positive Bcl-2 expression was similar to oral normal mucosa,but in the part of the lymphocytic infiltration of OLP, overexpression of Bcl-2 was observed. In the SCC, the Bcl-2 expression was significantly higher than that in normal oral mucosa(P<0.05). In the tissue of simple hyperplasia, mild dysplasia, moderate dysplasia, poorly differentiated SCC and erosive OLP, the expression of Bax was significantly higher than that in normal oral mucosa (P<0.05). CONCLUSIONS: Bax was closely related to the early event of LK carcinogenesis. Bcl-2 may not play a role in LK carcinogenesis. Bcl-2 and Bax play an important role in pathogenesis of OLP. We postulate that the Bcl-2 inhibits the apoptosis of lymphocytes that strengthen the cell-mediated immune process and the overexpression of Bax was related to the apoptosis of epithelial cells in OLP.

PMID: 15619691 [PubMed - in process]

Whitish papules and plaques on the tongue.

Am Fam Physician. 2004 Dec 15;70(12):2353-4

Authors: Khachemoune A, Ogholikhan M

PMID: 15617301 [PubMed - indexed for MEDLINE]

Transformation of proliferative verrucous leukoplakia to oral carcinoma: a ten years follow-up.

Med Oral. 2004 May-Jul;9(3):229-33

Authors: Navarro CM, Sposto MR, Sgavioli-Massucato EM, Onofre MA

The authors present a case of proliferative verrucous leukoplakia (PVL) in a 78-year-old man. It was initially presented as leukoplakia on the tongue but a microscopic investigation in 1991 revealed it to be a mild epithelial dysplasia. After 5 years of follow-up, the lesion presented changes in size and location, and a recidivant behavior. In 1996, a red granular and indurated area that appeared on the tongue was found to be a microinvasive squamous cell carcinoma when microscopically investigated. After a review of the clinicopathologic behavior of this entity, the authors concluded that it was a typical PVL, whose diagnosis is difficult and retrospective, as indicated by others. The authors emphasize the importance of periodic detailed clinical and histological examination of this type of lesions in order to detect early signs of malignancy.

PMID: 15122125 [PubMed - indexed for MEDLINE]

Alterations in plasma lipid profile patterns in head and neck cancer and oral precancerous conditions.

Indian J Cancer. 2004 Jan-Mar;41(1):25-31

Authors: Patel PS, Shah MH, Jha FP, Raval GN, Rawal RM, Patel MM, Patel JB, Patel DD

BACKGROUND: The changes in lipid profile have long been associated with cancer because lipids play a key role in maintenance of cell integrity. AIMS: The present study evaluated alterations in plasma lipid profile in untreated head and neck cancer patients as well as patients with oral precancerous conditions (OPC) and its association with habit of tobacco consumption. MATERIAL AND METHODS: This hospital-based case control study included 184 head and neck cancer patients, 153 patients with OPC and 52 controls. Plasma lipids including: (i) Total cholesterol, (ii) LDL cholesterol (LDLC), (iii) HDL cholesterol (HDLC) (iv) VLDL cholesterol (VLDLC) and (v) triglycerides were analysed by spectrophotometric kits. STATISTICAL ANALYSIS USED: Student's t-test was performed to compare mean values of the parameters. RESULTS: A significant decrease in plasma total cholesterol and HDLC was observed in cancer patients (P=0.008 and P=0.000 respectively) as well as in patients with OPC (P=0.014 and P=0.000, respectively) as compared to the controls. The plasma VLDL and triglycerides levels were significantly lower in cancer patients as compared to the patients with OPC (P=0.04) and controls (P=0.059). The tobacco habituates showed lower plasma lipid levels than the non-habituates. Our data strengthen the evidence of an inverse relationship between plasma lipid levels and head and neck malignancies as well as OPC. CONCLUSION: The lower levels of plasma cholesterol and other lipid constituents in patients might be due to their increased utilization by neoplastic cells for new membrane biogenesis. The findings strongly warrant an in-depth study of alterations in plasma lipid profile in head neck cancer patients.

PMID: 15105576 [PubMed - indexed for MEDLINE]

[The content of estradiol receptors in oral mucosa precancerous lesions and its effect]

Shanghai Kou Qiang Yi Xue. 1998 Dec;7(4):204-6

Authors: Yao H, Wu BX

OBJECTIVE:In order to clarify the content of estroen receptors (ER) in oral mucosa precancerous lesions and its effect on dignosis and treatment. METHODS: ER was measured by SP method in 19oral squamous cell carcinoma (SCC),20 oral leukoplakia(LK),21 oral lichen planus (LP) and 7 normal mucosa(NM). RESULTS: 42.86%,71.43%,60.00%,68.42% were ER positive in NM,LP,LK,SCC respectively. The postitive cells located in spinous layer.ER contents were no significance different in these four diseases.There was no relationship between ER content and pathologic staging. CONCLUSION: It showed that ER existed in SCC,LK,LP and NM,but it could not implicate for the carcinogenesis.Oral mucousal tumor is perhaps hormone depended.

PMID: 15071625 [PubMed - as supplied by publisher]

The influence of resection and aneuploidy on mortality in oral leukoplakia.

N Engl J Med. 2004 Apr 1;350(14):1405-13

Authors: Sudb&#xF8; J, Lippman SM, Lee JJ, Mao L, Kildal W, Sudbø A, Sagen S, Bryne M, El-Naggar A, Risberg B, Evensen JF, Reith A

BACKGROUND: Although the standard treatment of oral leukoplakia ranges from watchful waiting to complete resection, the value of these approaches is unknown. METHODS: We studied the relations among resection, ploidy status, and death from cancer in 103 patients with diploid dysplastic oral leukoplakia, 20 patients with tetraploid lesions, and 27 patients with aneuploid lesions. Data on cancer-specific mortality and treatment were obtained from the Cancer Registry of Norway, Statistics Norway, and chart reviews. RESULTS: Primary oral carcinoma developed in 47 of the 150 patients with leukoplakia (31 percent)--5 with diploid, 16 with tetraploid, and 26 with aneuploid leukoplakia--during a mean follow-up of 80 months (range, 4 to 237). The margin status of the initial leukoplakia resection had no relation to the development of oral cancer (P=0.95). Twenty-six of the 47 patients in whom cancer developed (4 with prior tetraploid and 22 with prior aneuploid lesions) had recurrences (55 percent); the recurrences were more frequently multiple and distant (within the oral cavity) among patients with aneuploid lesions than among those with tetraploid or diploid lesions. All 47 patients underwent a standard regimen of surgery and radiation, followed by chemotherapy in the 26 with recurrent cancer. Only patients with aneuploid leukoplakia died of oral cancer; the five-year rate of death from cancer was 72 percent. Aneuploidy-related first carcinomas were diagnosed at a more advanced stage than were carcinomas originating from diploid or tetraploid leukoplakia (P=0.03) and were more likely to be lethal regardless of the stage. CONCLUSIONS: Complete resection of aneuploid leukoplakia does not reduce the high risk of aggressive carcinoma and death from oral cancer.

PMID: 15070790 [PubMed - indexed for MEDLINE]

[Treatment of oral leukoplakia: Comparison of the results beteen cryosurgery and laser surgery]

Shanghai Kou Qiang Yi Xue. 1999 Jun;8(2):118-9

Authors: Zhang DN, Zhou GY, Zhao ZM

PMID: 15048293 [PubMed - as supplied by publisher]

Fatty acid synthase expression is induced by the Epstein-Barr virus immediate-early protein BRLF1 and is required for lytic viral gene expression.

J Virol. 2004 Apr;78(8):4197-206

Authors: Li Y, Webster-Cyriaque J, Tomlinson CC, Yohe M, Kenney S

The Epstein-Barr virus (EBV) immediate-early (IE) protein BRLF1 (R) is a transcription factor that induces the lytic form of EBV infection. R activates certain early viral promoters through a direct binding mechanism but induces transcription of the other EBV IE gene, BZLF1 (Z), indirectly through cellular factors binding to a CRE motif in the Z promoter (Zp). Here we demonstrate that R activates expression of the fatty acid synthase (FAS) cellular gene through a p38 stress mitogen-activated protein kinase-dependent mechanism. B-cell receptor engagement of Akata cells also increases FAS expression. The FAS gene product is required for de novo synthesis of the palmitate fatty acid, and high-level FAS expression is normally limited to liver, brain, lung, and adipose tissue. We show that human epithelial tongue cells lytically infected with EBV (from oral hairy leukoplakia lesions) express much more FAS than uninfected cells. Two specific FAS inhibitors, cerulenin and C75, prevent R activation of IE (Z) and early (BMRF1) lytic EBV proteins in Jijoye cells. In addition, cerulenin and C75 dramatically attenuate IE and early lytic gene expression after B-cell receptor engagement in Akata cells and constitutive lytic viral gene expression in EBV-positive AGS cells. However, FAS inhibitors do not reduce lytic viral gene expression induced by a vector in which the Z gene product is driven by a strong heterologous promoter. In addition, FAS inhibitors do not reduce R activation of a naked DNA reporter gene construct driven by the Z promoter (Zp). These results suggest that cellular FAS activity is important for induction of Z transcription from the intact latent EBV genome, perhaps reflecting the involvement of lipid-derived signaling pathways or palmitoylated proteins. Furthermore, using FAS inhibitors may be a completely novel approach for blocking the lytic form of EBV replication.

PMID: 15047835 [PubMed - indexed for MEDLINE]

Molecular evidence for rhesus lymphocryptovirus infection of epithelial cells in immunosuppressed rhesus macaques.

J Virol. 2004 Apr;78(7):3455-61

Authors: Kutok JL, Klumpp S, Simon M, MacKey JJ, Nguyen V, Middeldorp JM, Aster JC, Wang F

Epstein-Barr virus (EBV) is a human oncogenic herpesvirus associated with epithelial cell and B-cell malignancies. EBV infection of B lymphocytes is essential for acute and persistent EBV infection in humans; however, the role of epithelial cell infection in the normal EBV life cycle remains controversial. The rhesus lymphocryptovirus (LCV) is an EBV-related herpesvirus that naturally infects rhesus macaques and can be used experimentally to model persistent B-cell infection and B-cell lymphomagenesis. We now show that the rhesus LCV can infect epithelial cells in immunosuppressed rhesus macaques and can induce epithelial cell lesions resembling oral hairy leukoplakia in AIDS patients. Electron microscopy, immunohistochemistry, and DNA-RNA in situ hybridization were used to identify the presence of a lytic rhesus LCV infection in these proliferative, hyperkeratotic, or parakeratotic epithelial cell lesions. These studies demonstrate that the rhesus LCV has tropism for epithelial cells, in addition to B cells, and is a relevant animal model system for studying the role of epithelial cell infection in EBV pathogenesis.

PMID: 15016868 [PubMed - indexed for MEDLINE]

[Treatment of oral leukoplakia with chinese herbs(No.1) and transferrin factor]

Shanghai Kou Qiang Yi Xue. 2000 Mar;9(1):47-8

Authors: Zhu QQ, Yang H, Lin XG, Deng GM

PMID: 15014854 [PubMed - as supplied by publisher]