P21(WAF1/CIP1) PROTEIN EXPRESSION IN NORMAL, HYPERPLASTIC AND MALIGNANT ENDOMETRIUM. CORRELATION WITH HORMONE RECEPTOR STATUS, C-ERBB-2 ONCOPROTEIN, BCL-2 AND OTHER CELL CYCLE RELATED PROTEINS (RB, P53, KI-67, PCNA)

Ioachim E.1, Kitsiou E., Mitselou A., Zagorianakou N., Charalabopoulos K., Salmas M., Makrydimas G., Vougiouklakis Th.2, Agnantis N.J.

Summary. Defects in the mechanisms controlling the cell cycle are crucial in cell transformation and/or tumor progression. p21(waf1/cip1) is an inhibitor of cyclin-dependent kinases, induced by p53-dependent and p53-independent pathways, which can block progression through the cell cycle. p21(waf1/cip1) expression has been investigated immunohistochemically in a series of 115 endometrial carcinomas, 62 cases of endometrial hyperplasias, and 62 cases of normal endometium (33 in proliferative phase and 29 in secretoty). The association between p21(waf1/cip1) expression with hormone receptor status, c-erbB-2 and other cell cycle related proteins p53, Rb, Кi-67, PCNA) was assessed by univariate analysis. Nuclear p21 (waf1/cip1) expression was statistically higher in the group of carcinomas compared with normal proliferative (p = 0.005) and secretory (p = 0.0012) endometrium. In addition, this expression was higher in hyperplastic lesions compared with normal proliferative (p = 0.02) and secretory (p = 0.04) endometrium. A statistically significant positive relationship of p21(waf1/cip1) expression with progesterone receptor status (p = 0.007), p53 protein (p = 0.001), pRb (p < 0.0001) and the two proliferative associated indices Ki-67 and PCNA (p < 0.0001) was observed. These data indicate that the expression of p21(waf1/cip1) protein seems to be an early event in endometrial carcinogenesis and is strongly associated with other cell cycle related proteins.

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