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 persistenc e 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 proliferati ve and hyperplastic endometrium, while a weak signal was detected in s ecretory endometrium. Bcl-2 expression tends to decrease in staining i ntensity with progression from benign endometrium, including prolifera tive and hyperplastic endometrium, to endometrioid carcinoma and to mu cinous, clear cell and serous carcinomas of the endometrium. Bcl-2 per sistence was observed in the majority (65%) of endometrial carcinomas. We demonstrated a significant correlation of bcl-2 immunoreactivity w ith 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 sig nificant difference was detected in tumors of different stages. We con clude 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 sugge sts that failure to inactivate bcl-2 expression early in the developme nt of endometrial carcinoma may provide an opportunity for accumulatin g genetic mutations and evolution from a precursor lesion to invasive carcinoma.