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Xin Xie, MD, PhD; Ole Petter F. Clausen, MD, PhD; Morten Boysen, MD, PhD

Arch Otolaryngol Head Neck Surg. 2002;128:897-902.

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.

From the Department of Otolaryngology (Drs Xie and Boysen) and the Institute for Pathology (Drs Xie and Clausen), The National Hospital, University of Oslo, Oslo, Norway.

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