Aberrant p21(CIP1/WAF1) protein accumulation in head-and-neck cancer.

Erber R, Klein W, Andl T, Enders C, Born AI, Conradt C, Bartek J, Bosch FX
Int J Cancer. 1997 74 (4): 383-9

PMID: 9291426 · DOI:10.1002/(sici)1097-0215(19970822)74:4<383::aid-ijc4>3.0.co;2-r

p21(CIP1/WAF1) is an inhibitor of cyclin-dependent kinases and, in normal tissues including squamous epithelia, has been associated with cell-cycle exit and differentiation. As shown in this pilot study, however, the majority of head-and-neck squamous-cell carcinomas (HNSCC) display aberrant p21(CIP1/WAF1) expression: of 42 tumors analyzed by immunohistochemical staining, 28 (67%) over-expressed the p21(CIP1/WAF1) protein. Accumulation of p21(CIP1/WAF1) was independent of the histological grade of the tumors as well as the genetic status of the p53 gene. In many cases, most notably in poorly differentiated or undifferentiated HNSCC, p21(CIP1/WAF1)-positive cells were actively proliferating tumor cells, since they also expressed proliferating-cell nuclear antigen (PCNA) and Ki-67. Accumulation of p21(CIP1/WAF1) occurred through a post-transcriptional mechanism since, in contrast to immunohistochemical analysis of the p21(CIP1/WAF1) protein, in situ hybridization showed no increase of mRNA levels as compared with cells in normal mucosa (n = 25). Clinically, among the patients with p21(CIP1/WAF1)-over-expressing tumors, there was increased recurring disease (p = 0.03; chi2-test), shortened disease-free survival (p = 0.0019; log-rank test) and shortened overall survival (p = 0.0071; log-rank test). These in vivo data indicate that in many HNSCC, accumulated p21(CIP1/WAF1) is compatible with increased tumor-cell proliferation, and they provide preliminary evidence that p21(CIP1/WAF1) may be of prognostic and predictive significance.

MeSH Terms (21)

Biopsy Blotting, Western Carcinoma, Squamous Cell Cyclin-Dependent Kinase Inhibitor p21 Cyclins Disease-Free Survival Enzyme Inhibitors Epithelial Cells Epithelium Genes, p53 Head and Neck Neoplasms Humans Immunohistochemistry In Situ Hybridization Mutation Predictive Value of Tests Reference Values RNA, Messenger Survival Rate Time Factors Transcription, Genetic

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