BCL-2 IS DOWN-REGULATED IN ATYPICAL ENDOMETRIAL HYPERPLASIA AND ADENOCARCINOMA

The bcl-2 protein, which protects cells from apoptosis, is normally ex pressed in a number of adult tissues. Dysregulated bcl-2 expression, s econdary to (14;18) chromosomal translocation, seems to promote the de velopment of follicular lymphomas, and recent findings of bcl-2 protei n in several solid tumors suggest that it might contribute to the gene sis of many other neoplasms, bcl-2 is also highly expressed in normal proliferative endometrium and markedly down-regulated in secretory end ometrium, which suggests that its expression is estrogen regulated, Be cause the development of most endometrial carcinomas is associated wit h hyperestrogenic states, we began the investigation of the role of bc l-2 in endometrial carcinogenesis by immunohistochemically quantifying its expression in proliferative, hyperplastic, atypically hyperplasti c, and carcinomatous endometrium. The results of this study show that bcl-2 is relatively highly expressed in proliferative (n = 11) and hyp erplastic (n = 18) endometrium, with respective mean staining scores o f 3.59 and 3.47 (scale, 0-4), but is significantly (P < 0.001) down-re gulated in atypical hyperplasia (a = 11; score, 0.82), and adenocarcin oma (n = 34; score, 0.86), bcl-2 expression did not correlate with sta ge, grade, estrogen-receptor, or progesterone-receptor expression, Pol ymerase chain reaction analyses of DNA isolated from several endometri al carcinomas were negative for (14;18) translocation involving the bc l-2 gene. Thus, bcI-2 apparently plays no role in the progression of a typical hyperplasia to carcinoma or in the development of high-grade o r advanced-stage endometrial carcinoma. These results, however, do not rule out the involvement of bcl-2 in very early, preatypical hyperpla sia phases of endometrial carcinogenesis. Finally the marked differenc e in bcl-2 expression in hyperplastic and atypically hyperplastic glan ds might prove to be diagnostically useful in the often difficult dist inction of these entities.