BRCA1 expression in leukoplakia and carcinoma of the tongue.

BACKGROUND AND OBJECTIVES: Expression of BRCA1 was examined in patients with leukoplakia and carcinoma of the tongue. Its prognostic value was evaluated in patients with tongue cancer. METHODS: Expression of BRCA1 was studied by immunohistochemical localization. Cytoplasmic staining of BRCA1 was observed in both leukoplakia and carcinoma of the tongue. RESULTS: In leukoplakia, 61% and 39% of the patients expressed BRCA1 expression with a staining intensity of 1+ and 2+, respectively. In patients with hyperplasia (67%), BRCA1 expression with a staining intensity of 1+ was 67%; BRCA1 expression with a staining intensity of 2+ was 33%. In patients with dysplasia (33%; mild and moderate), BRCA1 expression with a staining intensity of 1+ and 2+ was 50% each. In carcinoma of the tongue, only 34% of the patients showed BRCA1 expression. In this group, 33% of the tumors exhibited 1+ staining, and only 1% of the tumors expressed 2+ staining. Moreover, BRCA1 expression with a staining intensity of 2+ was significantly higher in patients with dysplasia (50%) than in those with hyperplasia (33%), followed by patients with squamous cell carcinoma of the tongue (1%). The percentage positivity of BRCA1 expression in tongue cancer patients was significantly lower (34%), as compared with patients with leukoplakia (100%; P = 0.000001). A significant positive correlation was noted between BRCA1 and c-myc (P = 0.012). Univariate survival analysis by log-rank test and multivariate survival analysis by Cox regression showed that BRCA1 expression was the most significant prognostic factor predicting relapse-free survival of early-stage patients. CONCLUSIONS: Subcellular localization of the BRCA1 gene product provided evidence of its involvement in the pathogenesis of tongue tumors.

Prognostic significance of biomarkers in squamous cell carcinoma of the tongue: multivariate analysis.

BACKGROUND AND OBJECTIVES: Expression of a panel of biomarkers, such as p53, Bcl-2, Cyclin D1, c-myc, p21ras, c-erb B2, cytokeratin-19 (CK-19), and factor VIII-related antigen (FVIII-RA), was studied together in anterior tongue tumors from the oral cavity and in posterior tongue tumors from the oropharynx of patients with early- and locally advanced-stage disease, to evaluate their prognostic value. METHODS: The expression of the above-mentioned biomarkers was studied by immunohistochemical localization. RESULTS: In this study, 18%, 26%, 62%, 75%, 73%, 50%, and 29% of the tumors exhibited p53, Bcl-2, Cyclin D1, c-myc, p21ras, c-erb B2, and CK-19 expression, respectively. Twenty percent of the tumors had a microvessel count of >0.0. The expression of these biomarkers was also correlated with clinicopathologic parameters. In early-stage patients with a tobacco habit, who showed borderline significance for relapse-free survival by Kaplan-Meier survival analysis, this turned out to be significant, with the general linear model univariate survival analysis. In the total group, disease stage emerged as the most significant prognostic factor, followed by c-myc, when Cox forward stepwise regression and general linear model multivariate survival analysis were performed. However, Cyclin D1, which was significant by Cox forward stepwise regression analysis, lost its significance by general linear model multivariate analysis. In patients with early-stage disease, MVC, which was a significant predictor of disease relapse by Cox forward stepwise regression analysis, lost its significance by general linear model analysis because of small number of patients. In patients with locally advanced tongue cancer, multivariate survival analysis of individual biomarkers by both Cox forward stepwise regression and general linear model analysis indicated c-myc expression to be strongly indicative of poor prognosis. However, multivariate analysis of individual markers along with a combination of markers showed that only by Cox forward stepwise regression analysis did the combined expression of markers c-myc, Cyclin D1, and p21ras emerge as a significant independent prognosticator. CONCLUSIONS: Overall stage emerged as the most significant prognostic indicator of disease outcome. Tobacco habit also affected relapse-free survival in patients with early-stage disease. However, immunostaining of c-myc in the tumors of locally advanced-stage tongue cancer patients might be a potential adjunct to clinical stage in the pathologic evaluation of tongue specimens.

Clinical usefulness of telomerase activation and telomere length in head and neck cancer.

BACKGROUND: Telomere shortening at every replication cycle is postulated to limit the life span of human somatic cells. In contrast, activation of telomerase is proposed to be an essential step for cancer cell immortalization. Head and neck cancer is the most common malignancy in the Indian population compared with Western countries. However, there are very few reports on telomerase activity and telomere length in head and neck cancer. METHODS: Telomerase activation and telomere length alterations were studied in tumor and adjacent normal tissues in 110 patients with head and neck cancer and 40 patients with precancerous/benign conditions. Telomerase activity and telomere lengths were determined by Telomeric Repeat Amplification Protocol (TRAP assay) and Southern blot analysis, respectively. RESULTS: Telomerase activation was observed in 78.2% of the malignant tissues, 85% of the precancerous tissues, and 53.1% of the adjacent normal tissues. Peak terminal restriction fragment length (TRF) was observed to be significantly lower in malignant tissues compared with the adjacent normal tissues. No significant correlation could be observed between telomerase activation and clinicopathologic characteristics of the patients. Two-year disease-free survival analysis showed that patients showing telomerase activation in the adjacent normal tissues and patients showing higher telomere length in malignant tissues had poor disease-free survival. CONCLUSIONS: Our results demonstrate the significant clinical usefulness of telomerase activation and telomere length for head and neck cancer patients. These markers may be helpful in predicting the clinical course of the disease and thus in identifying the patients in need of a close follow-up and vigorous adjuvant treatment.

Primary malignant large bowel lymphoma.

Primary gastrointestinal (GI) lymphomas constitute about 5.6 per cent of total gut neoplasms. The involvement of large bowel as primary site is all the more rare. We carried out this study to evaluate the prevalence and clinicopathological features of large bowel lymphoma at Gujarat Cancer and Research Institute and to compare our findings with published literature. We carried out a retrospective analysis of the records of histologically diagnosed cases of large bowel lymphoma over a 5 year period. A total of eight cases of large bowel lymphoma were identified compared with 57 cases of primary GI lymphoma of other sites, constituting about 12.3 per cent (eight of 65) of all GI lymphomas. Peak incidence was observed in the second decade of life with a mean age at presentation of 30.6 years (range 4-70 years). A male-to-female ratio of one to two was observed. The most commonly presenting feature was altered bowel habits and diarrhea in more than 50 per cent of the patients. One patient presented with acute intestinal obstruction. Diagnosis was made by colonoscopic biopsies in all but one case. All of the patients were treated with surgery and adjuvant chemotherapy. A 4-year disease-free survival of 66.7 per cent was observed (95% confidence interval 0.05-1.28). There was no significant difference in survival in patients with high-grade versus low-grade tumors (50% vs 66.7%; P = 0.88) and stage of disease (75% vs 50%; P = 0.45) in stage II and III respectively. We conclude that large bowel lymphoma is a curable disease if treated aggressively. We suggest that all patients should be treated by primary surgery and should receive adjuvant chemotherapy.

Solitary extramedullary plasmacytoma - larynx.

Solitary Plasmacytoma of the larynx is a rare tumor with male predominance and most patients are between 50-70 years of age. The paper reports a case of Solitary Extramedullary' Ipasmacytoma. (EMP) ljirynx in subglottic region, in a 65-year-old man successfully treated with complete response to radiotherapy.

Vitamin B(12) and Folate Status in Head and Neck Cancer.

Deficiency of vitamin B(12) and folate is associated with causation of certain precancerous conditions and cancer. The present study was carried out on 56 controls, 167 patients with oral precancerous conditions (OPC) and 214 head and neck cancer patients, to evaluate the plasma vitamin B(12) and folate levels to determine their association with tobacco habits and vegetarianism and several sociodemographic factors. The subjects were interviewed using a health habit and diet questionnaire at the time of blood collection. Simultaneous estimations of plasma vitamin B(12) and folate were done by Dual Count Radioassay. It was found that the habit of tobacco consumption, lower education and low income were among the risk factors. A decrease in the plasma vitamin B(12) and folate levels with respect to tobacco habits, disease progression, and vegetarian diet was also observed. The individuals in the ower quartile for vitamin B(12) and folate were at a higher risk of developing OPC, as compared to those in higher quartiles. Similarly, the patients with OPC in lower quartiles were found to be at a higher risk of developing cancer than their counterparts. There was a significant positive correlation between vitamin B(12) and folate levels in the subjects consuming tobacco, and more so in patients with OPC (r=0.4330, p=0.000). Folate levels were significantly lower in patients with advanced as compared with early disease (ANOVA p=0.006 and Spearman's Rho = -0.211 and p=0.01). The results suggest, potential significance of plasma vitamin B(12) and folate levels in head and neck malignancies which needs to be confirmed by further studies on a large population.

Role of Dietary Intake and Biomarkers in Risk of Breast Cancer: A Case Control Study.

Reproductive factors are not considered to play a significant role in the aetiology of breast cancer in low incidence regions like Gujarat, although it is well established that they exert a major influence on such tumours in the western developed world. Women in the western Indian region have a very low prevalence of smoking, alcohol consumption but a high prevalence of vegetarianism. Noting the changes in the life style practices with increasing affluence is likely to yield several interesting findings in such a population. Physical activity and dietary factors have emerged as important parameters and their lack may contribute significantly to the risk of breast cancers. The breast cancer risk significantly increased with higher consumption of total fat (>25% of total calories), frequent intake of fried foods and sweets. A significant protection was offered by frequent consumption of green yellow leafy vegetables, foods rich in b-carotene and isoflavonoids. The present study demonstrated a good protective effect of dietary intake of antioxidant vitamins. The breast cancer risk increases with elevation of circulating lipid components except HDL-cholesterol.

A Study of Various Sociodemographic Factors and Plasma Vitamin Levels in Oral and Pharyngeal Cancer in Gujarat, India.

Present study examined various socio-demographic factors, dietary patterns, habit of tobacco consumption and plasma vitamin levels in 56 healthy individuals, 146 patients with oral precancerous conditions (OPC) and 132 untreated oral and pharyngeal cancer patients. The subjects were interviewed with a detailed health, habit and diet questionnaire. Plasma b-carotene, vitamin-A and vitamin-E levels were determined spectrophotometrically. An increased incidence of OPC was observed in the age group of <30 years which was associated with tobacco chewing. Whereas, incidence of cancer was in the age group of 30-60 years where habit of tobacco smoking was more prevalent. Majorities of the subjects were from rural area, poor, unaware about association of diet with cancer. The body mass index was lower (p=0.045) in patients with OPC and cancer patients as compared to the controls. Plasma b-carotene and vitamin-E levels were lower in patients with OPC (p=0.000 and 0.031, respectively) and untreated cancer patients (p=0.000 and 0.071, respectively) than the controls. ROC curve revealed that plasma vitamin levels have ability to discriminate between controls and cancer patients. Lower plasma b-carotene and vitamin-E levels were observed in tobacco consumers as compared to non-consumers. Odds ratio revealed that controls and patients with OPC having tobacco habit and lower plasma levels of b-carotene were at a higher risk (p<0.05) of developing cancer. Regression study and Analysis of Variance revealed that plasma b-carotene levels were inversely associated (r(2)=0.14, p=0.001 and F=0.000, respectively) with increase in the stage of cancer. The data provide interesting clues of potential role of diet, tobacco habits, socio-demographic status and plasma vitamin levels in etiology of oral and pharyngeal cancer in Gujarat, where no such findings are reported.