Persistent expression of bcl-2 onco-protein in endometrial carcinoma correlates with hormone receptor positivity

The protein product of proto-oncogene bcl-2 is thought to be involved in inhibition of apoptosis and is hormonally regulated in a variety of in vitro and in vivo experiments. The association of bcl-2 persistence and hormone receptor status was investigated by immunocytochemistry from paraffin-embedded tissue in a series of 82 women with endometrial carcinoma and 20 women with benign endometrium. In benign endometrium, bcl-2 immunoreactivity was strongly present in glands of proliferative and hyperplastic endometrium, while a weak signal was detected in secretory endometrium. Bcl-2 expression tends to decrease in staining intensity with progression from benign endometrium, including proliferative and hyperplastic endometrium, to endometrioid carcinoma and to mucinous, clear cell and serous carcinomas of the endometrium. Bcl-2 persistence was observed in the majority (65%) of endometrial carcinomas. We demonstrated a significant correlation of bcl-2 immunoreactivity with estrogen receptor (P=0.000005) and progesterone receptor status (P=0.00032). The bcl-2 persistence was found to be significantly higher in FIGO G1 and G2 tumors than in G3 tumors (P = 0.00035), while no significant difference was detected in tumors of different stages. We conclude that bcl-2 persistence is highly correlated with the presence of hormone receptors and may be hormone-dependent or related to hormonal regulation in endometrial carcinomas. Persistent expression of bcl-2 in normal and hyperplastic endometrium and endometrial carcinoma suggests that failure to inactivate bcl-2 expression early in the development of endometrial carcinoma may provide an opportunity for accumulating genetic mutations and evolution from a precursor lesion to invasive carcinoma.