Apoptosis index is a predictor of metastatic phenotype in patients with early stage squamous carcinoma of the tongue - A hypothesis to support this paradoxical association

BACKGROUND, Patients with squamous carcinoma of the oral tongue in clinical stages TIN0M0 and T2N0M0 with a tumor thickness less than or equal to 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 apop totic index (AI), the proliferation index, and tumor grade in relation to L N metastasis in patients with early stage squamous carcinoma of the oral to ngue. 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 wer e evaluated for tumor grade, AI (by using the terminal deoxynucleotidyl tra nsferase-mediated dUTP nick-end labeling technique), and proliferation inde x (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 neg ative subgroups did not differ in the mean PCNA index, and there was no sig nificant difference in the distributions of turner grade between LN positiv e and LN negative subsets. Four of 12 tumors with an AI less than or equal to 5% and 10 of 11 tumors with an AI > 5%, had LN metastasis (P = 0.009; ri sk ratio, 20). The AI maintained its significance with respect to LN metast asis in the multivariate analysis (P = 0.003). The ii-year recurrence free survival was significantly better in patients with tumors that had an AI va lue less than or equal to 5% compared with patients with tumors that had an Al > 5% (92% vs. 32%) (P = 0.033). However, the Al lost its impact on recu rrence free survival within a Cox proportional hazards model (P = 0.068). CONCLUSIONS. A higher hi value is a predictor of LN metastasis and may serv e as a prognostic factor in patients with early stage squamous carcinoma of the oral tongue. The authors present a hypothesis to explain this rather s urprising finding. (C) 2001 American Cancer Society.