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Immunohistochemical study of apoptosis-related Bcl-2 protein and its correlation with proliferation indices (Ki67, PCNA), tumor suppressor genes (p53, pRb), the oncogene c-erbB-2, sex steroid hormone receptors and other clinicopathological features, in normal, hyperplastic and neoplastic endometrium

The bcl-2 gene codes for a protein which functions to inhibit apoptotic cell death, that involves an intrinsic normal cell death program. Bcl-2 overexpression was originally described in a follicular lymphoma, but more recently bcl-2 expression has been observed in a variety of other human neoplasms. Variation in the frequency of apoptosis in hormone-sensitive tissues, such as the endometrium, is known to occur as a result of hormonal changes in both physiological and pathological circumstances. In this study we examined bcl-2 protein expression in a total of 170 samples of endometrial tissues (18 proliferative endometrium, 14 secretory endometrium, 35 adenomatous hyperplasia and 103 carcinomas). The results were compared with p53, pRb and c-erbB-2 proteins expression, estrogen and progesterone receptors status, with the proliferative activity and with clinicopathological features. The expression of bcl-2 protein was lower in the group of carcinomas, when compared with the cases of adenomatous hyperplasia (p < 0.0001), normal proliferative (p < 0.0001) and secretory endometrium (p = 0.07). In normal proliferative endometrium bcl-2 expression was correlated with PCNA (p = 0.026) and in secretory endometrium it was correlated with ER status (p = 0.042). In hyperplasias, bcl-2 was correlated with PCNA (p = 0.019) and the PR (p = 0.007) expression. In carcinomas, decreased bcl-2 expression was associated with increased tumor grade (p = 0.04). A positive relationship between bcl-2 expression and pRb, as well as PCNA score (p = 0.014 and p = 0.001, respectively), was also found. These results indicate that bcl-2 expression may play a role in the inhibition of apoptosis in endometrial carcinoma and its expression seems to be associated with tumor differentiation and cell proliferation.