BCL-2 EXPRESSION AND PROGNOSIS OF PATIENTS WITH ENDOMETRIAL CARCINOMA

Bcl-2 protein inhibits apoptosis, reduces the requirement for growth f actors, and thereby extends the survival of cells. Recent findings of Bcl-2 in several solid tumors suggest that it might contribute to the genesis of some types of cancer. Over-expression of Bcl-2 might play a role in carcinogenesis and malignant progression of endometrial carci noma. The aims of this study were to determine Bcl-2 expression in end ometrial carcinoma in relation to other histopathologic prognostic fac tors, and to test its prognostic significance in patients with endomet rial carcinoma. A total of 61 endometrioid-type endometrial carcinomas were immunohistochemically investigated for Bcl-2 expression on cryos tat sections. Bcl-2 localization was observed in cytoplasm in 18 tumor s, in nucleus in 27 tumors, or in both in 5 tumors. In 11 tumors, Bcl- 2 was observed neither in cytoplasm nor in nucleus. There was not a st atistically significant relationship between grade of tumor and Bcl-2 expression, Cytoplasmic Bcl-2 became less frequently expressed as the tumor invaded the myometrium deeper (P < 0.025), Retroperitoneal lymph node dissection was performed in 57 patients. Multiple-regression anal ysis showed that lymph-vascular space invasion and nuclear expression of Bcl-2 were correlated to pelvic lymph-node metastasis (p < 0.0001 a nd < 0.05 respectively). Univariate Cox regression analysis revealed t hat nuclear Bcl-2 expression was associated with shorter survival (p < 0.05) than that of patients with cytoplasmic Bcl-2 expression. Pelvic node metastasis was a significant prognostic factor for patients who underwent systematic retroperitoneal lymph node dissection. Cox multiv ariate-regression analysis revealed that pelvic node metastasis and ce rvical invasion were the most important prognostic factors in this ser ies of patients, When the analysis was made after exclusion of pelvic node metastasis, histologic grade (hazard ratio = 2.4), cervical invas ion (hazard ratio = 3.7) and nuclear Bcl-2 expression (hazard ratio = 11.5) were shown to be significant predictors of survival of the patie nts. These results indicate that aberrant Bcl-2 expression might be in volved in malignant progression of endometrioid-type endometrial carci noma. Site of Bcl-2 localization may be an important predictor of prog nosis for patients with endometrioid-type endometrial carcinoma. (C) 1 998 Wiley-Liss, Inc.