The two well-defined pathways that are shown to be prominently altered in a variety of cancers are the cell cycle regulatory pathways led by either p53 or Rb genes. The present study is undertaken to find the pathway that is more altered in oral carcinoma at protein level, with special emphasis on its prognostic significance. The expression pattern of key molecules of the Rb and p53 pathways, such as Rb, cyclin D1, CDK4, p16, p53, p21 and Bcl-2 and the proliferative marker PCNA were analysed in 348 oral carcinoma specimens by immunohistochemical technique. The expression index of these molecules and various clinicopathological factors were statistically correlated with treatment end points to assess its prognostic efficacy after following up these patients up to a maximum of 48 months with a median of 23 months. Rb pathway proteins, Rb (P ¼ 0.016), cyclin D1 (P ¼ 0.0001) and p16 (P ¼ 0.012) showed significant association with disease-free survival, and p16 (P ¼ 0.041) and cyclin D1 (P ¼ o0.0001) with the overall survival. Among p53 pathway proteins studied, only p53 expression index showed association with both disease-free survival and overall survival. Multivariate analyses confirmed that the biological variables, cyclin D1 and p16 and the clinical variable, 'stage of disease' were independent predictors of disease-free survival and overall survival. Subgrouping of the patients on the basis of p16 and cyclin D1 expression revealed that the subgroup having downregulation of p16 and overexpression of cyclin D1 exhibited the worst disease-free survival and overall survival compared to the other subgroups. The present data showed that disabling of the Rb and p53 pathways were frequent events in oral carcinoma. The study also demonstrated that the Rb pathway proteins are comparatively more important than p53 pathway proteins for the prognostication of oral carcinoma patients. The combined evaluation of p16 and cyclin D1 in oral carcinoma could identify a group of patients with the worst survival who might therefore need alternate or more intense treatment strategies. Oral cancer is one of the 10 most common cancers in the world and is commonest in India and other south-east Asian countries.1 In India, oral cancer is highly prevalent, comprising a large fraction of all malignancies, due to the habit of tobacco chewing alone or with betel quid, which is commonly observed in the population.2 Although recent advances have reduced the morbidity of oral cancer, the 5-year survival rate for these patients has remained almost unchanged at B50% for the last 30 years.3 Oral cancers are highly heterogeneous in nature regarding site, biology and treatment response. In clinical practice, the treatment planning and prognosis of oral cancer is mainly based on the TNM classification; however, there is increasing evidence that in its current form, it is probably insufficient to predict the clinical outcome of patients with oral carcinoma. Therefore, it is important to look for new biological prognostic markers that might add inform...

Thus, tongue and buccal cancers represent different biological subentities, and such differences should be considered in oral cancer management.

BACKGROUND Patients with squamous carcinoma of the oral tongue in clinical stages TIN0M0 and T2N0M0 with a tumor thickness ≤ 3 mm usually do not have lymph node (LN) metastasis. However, factors that are useful in predicting LN metastasis in thicker tumors (> 3 mm thick) need to be identified. The authors investigated the clinical relevance of the apoptotic index (AI), the proliferation index, and tumor grade in relation to LN metastasis in patients with early stage squamous carcinoma of the oral tongue. METHODS Twenty‐three patients with squamous carcinoma of the anterior two‐thirds of the tongue measuring < 2 cm in height and > 3 mm in thickness were evaluated for tumor grade, AI (by using the terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling technique), and proliferation index (by proliferating cell nuclear antigen [PCNA] expression). RESULTS The mean AI value was significantly higher in LN positive patients compared with LN negative patients (P = 0.012). The LN positive and LN negative subgroups did not differ in the mean PCNA index, and there was no significant difference in the distributions of tumor grade between LN positive and LN negative subsets. Four of 12 tumors with an AI ≤ 5% and 10 of 11 tumors with an AI > 5% had LN metastasis (P = 0.009; risk ratio, 20). The AI maintained its significance with respect to LN metastasis in the multivariate analysis (P = 0.003). The 4‐year recurrence free survival was significantly better in patients with tumors that had an AI value ≤ 5% compared with patients with tumors that had an AI > 5% (92% vs. 32%) (P = 0.033). However, the AI lost its impact on recurrence free survival within a Cox proportional hazards model (P = 0.068). CONCLUSIONS A higher AI value is a predictor of LN metastasis and may serve as a prognostic factor in patients with early stage squamous carcinoma of the oral tongue. The authors present a hypothesis to explain this rather surprising finding. Cancer 2001;91:578–84. © 2001 American Cancer Society.

A higher AI value is a predictor of LN metastasis and may serve as a prognostic factor in patients with early stage squamous carcinoma of the oral tongue. The authors present a hypothesis to explain this rather surprising finding.

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