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Prognostic Significance of p21WAF1/CIP1 Expression in Tongue Squamous Cell Carcinomas
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 p21WAF1/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 p21WAF1/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 p21WAF1/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 p21WAF1/CIP1 values had increased disease-specific survival time (P = .03). The correlation between p21WAF1/CIP1
expression and disease-specific survival was even more significant when restricted
to p53-negative tumors (P = .002). A 2-parameter
combination between p21WAF1/CIP1 expression and Bax expression
or p21WAF1/CIP1 expression and p53 accumulation, respectively,
revealed an enhanced prognostic potential (P<.001)
when compared with single parameters.
Conclusion The expression of p21WAF1/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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