P53 PROTEIN IN ENDOMETRIAL CANCER IS RELATED TO PROLIFERATIVE ACTIVITY AND PROGNOSIS BUT NOT TO EXPRESSION OF P21 PROTEIN

Expression of the tumor suppressor gene product p53 and the cyclin-dep endent kinase inhibitor p21, which is transcriptionally activated by p 53, was investigated and compared with patient survival in a retrospec tive longitudinal study of 202 cases of endometrial carcinoma. The med ian duration of follow-up was 4.3 years. P53 was observed immunohistoc hemically in 63 (31%) of the tumors and was found by univariate analys is to be related to reduced adjusted survival (p = 0.00028) and diseas e-free survival (p = 0.04). However, p53 expression was not found by m ultivariate analysis to be an independent prognostic factor when compa red with FIGO stage, histologic grade, and proliferative activity, as determined by immunoreactivity for topoisomerase II alpha with the ant ibody Ki-S1. Overexpression of p53 was related to histologic grade (p < 0.00001), proliferative activity (p = 0.0071), and inversely to prog esterone receptor content (p = 0.042). Immunohistochemical identificat ion of p21 was investigated in 95 cases and found to be positive in 19 (39%) of 49 tumors with p53 overexpression and in 13 (28%) of 45 tumo rs without p53 overexpression (p = 0.28). Expression of p21 is therefo re not related to p53 expression, nor was it found to be related to pr oliferative activity. Strong expression of p21 was observed in tumors negative for progesterone receptors (p = 0.0028). P53 in endometrial c arcinoma is not associated with induction of the cell cycle inhibitor p21, but is associated with an enhanced proliferative activity. The fi ndings of multivariate analysis suggest that the prognostic significan ce of p53 is related mainly to cell proliferation.