Prognostic impact of p21/waf1/cip1 in colorectal cancer

In addition to the tumor suppressor gene P53, Cyclin Dependent Kinases (CDK ) are well known to influence the cell cycle in normal human tissues and va rious neoplasias as well. The purpose of our present study was to evaluate the expression of the CDK-inhibitor p21/waf1/cip1 in colorectal cancer with special emphasis on the prognostic impact. Between 1985 and 1991, 294 pati ents (median age, 65 years) underwent surgical operative therapy for colore ctal cancer. For malin-fixed and paraffin-embedded tumor specimens were inv estigated. For immunohistochemistry the Catalysed Reporter Deposition (CARD ) technique was performed, The survival propability was calculated and poss ible prognostic risk factors were tested using multivariate analysis. The p 21/ waf1/cip1 staining pattern was positive in 197 (67%) specimens and nega tive in 97 (33%) samples. No significant correlation could been calculated between p21/waf1/cip1 expression and other variables such as age, sex, WHO- Classification, localisation, grading, TNM-classification or UICC-stage. Pa tients with a positive staining reaction had a significantly better surviva l (p < 0.0052). Moreover, p21/waf1/cip1 was shown to be an independent prog nostic parameter by multivariate analysis (p < 0.022). In contrast with the se findings, the p53 tumor status had no impact on survival. P21/waf1/cip1 appears to be an independent prognostic parameter in colorectal cancer and is associated with a favorable survival. This feature may be related to a c ell cycle arrest in the G(1), phase induced by p21/waf1/cip1, resulting in lower tumor cell proliferative activity. (C) 2000 Wiley-Liss, Inc.