Prognostic significance of p21WAF1/CIP1 expression in tongue squamous cell carcinomas

Objective: To investigate the prognostic significance of p21(WAF1/CIP1) expression and its relationship with p53 accumulation and other apoptotic markers such as Bax, Bcl-2, and apoptotic index in relation to disease-specific survival in oral tongue squamous cell carcinoma (SCC). Design: A 10-year retrospective clinical study. Information about clinical findings, treatment, and follow-up has been recorded prospectively. Patients and Methods: Diagnostic, formalin-fixed, paraffin-embedded sections taken from 80 randomly selected patients before treatment for T I to T5 oral tongue SCC were stained immunohistochemically with p21(WAF1/CIP1). The percentages of positive nuclei that stained positive for tumor were determined. Main Outcome Measures: The significance of prognostic parameters was tested by log-rank and Kaplan-Meier methods for the univariate analysis. The Cox proportional hazards regression model was used for multivariate analysis. Results: Expression of p21(WAF1/CIP1) correlated inversely with T classification and clinical stage (P=.02 and P=.006, respectively) but not with N classification, tumor differentiation, or apoptosis-related variables such as p53 accumulation, apoptotic index, and Bax and Bcl-2 expression. Patients with tumor's expressing high p21(WAF1/CIP1) values had increased disease-specific survival time (P=.03). The correlation between p21(WAF1/CIP1) expression and disease-specific survival was even more significant when restricted to p53-negative tumors (P=.002). A 2-parameter combination between p21(WAF1/CIP1) expression and Bax expression or p21(WAF1/CIP1) expression and p53 accumulation, respectively, revealed an enhanced prognostic potential (P<.001) when compared with single parameters. Conclusion: The expression of p21(WAF1/CIP1), particularly in combination with p53 accumulation or Bax expression, has prognostic value in oral tongue SCC.