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Prognostic significance of p21WAF1/CIP1 expression in tongue squamous cell carcinomas
Xin Xie1, Ole Petter F Clausen, Morten Boysen
1Department of Otolaryngology and the Institute for Pathology, The National Hospital, University of Oslo, Norway. xin.xie@labmed.uio.no
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 T1 to T4 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 tumors 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.
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