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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)
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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