Premium
Aberrant p21 CIP1/WAF1 protein accumulation in head‐and‐neck cancer
Author(s) -
Erber Ralf,
Klein Wolfgang,
Andl Thomas,
Enders Christel,
Born Antonio I.,
Conradt Christian,
Bartek Jiri,
Bosch Franz X.
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970822)74:4<383::aid-ijc4>3.0.co;2-r
Subject(s) - head and neck , head and neck cancer , medicine , biology , cancer research , cancer , oncology , genetics , pathology , surgery
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 differ‐ entiated 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 hybrid‐ ization 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; χ 2 ‐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. Int. J. Cancer 74:383–389, 1997. © 1997 Wiley‐Liss, Inc.