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).


METHODS
A 10-year retrospective clinical study. Information about clinical findings, treatment, and follow-up has been recorded prospectively.


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.


METHODS
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.


CONCLUSIONS
The expression of p21(WAF1/CIP1), particularly in combination with p53 accumulation or Bax expression, has prognostic value in oral tongue SCC.
Xie
Xin
X
Department of Otolaryngology and the Institute for Pathology, The National Hospital, University of Oslo, Norway. xin.xie@labmed.uio.no
Clausen
Ole Petter F
OP
Boysen
Morten
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis* / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000032:analysis*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D019254:Genes, bcl-2 / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D012189:Retrospective Studies; D015996:Survival Rate; D014062:Tongue Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein