P53 OVEREXPRESSION AND BCL-2 PERSISTENCE IN ENDOMETRIAL CARCINOMA - COMPARISON OF PAPILLARY SEROUS AND ENDOMETRIOID SUBTYPES

Forty-two cases, including 21 uterine papillary serous carcinomas (UPS C) and 21 age-, nuclear-grade-, and clinical-stage-matched uterine end ometrioid carcinomas (UEC), were studied immunohistochemically for p53 and bcl-2 in archival paraffin-embedded tissue. Compared to UEC (28.6 % positive), UPSC (71.4% positive) had a significantly higher frequenc y of p53 overexpression (P = 0.005); furthermore, in a clinical-stage- matched fashion, a higher frequency of p53 overexpression was found in early-stage cases (P = 0.032), but not in late-stage cases. In a nucl ear-grade-matched comparison, no statistical difference in p53 overexp ression was identified between the two subtypes, although UPSC had str onger p53 immunoreactivity than UEC. Of UPSC, no difference in p53 ove rexpression was detected between tumors of early and late stages; addi tionally, in 5 cases, there was an abrupt transition from nonstaining morphologically benign glands to uniformly positive p53 nuclear staini ng in regions of intraepithelial carcinoma. Conversely, in UEC, there was a significant difference in p53 immunostaining between tumors of e arly and late stages (P = 0.01); no case had an abrupt transition for p53 immunostaining. For bcl-2 immunostaining, UEC had a significantly higher immunohistochemical staining score than did UPSC (P = 0.0002). In general, the staining intensity of bcl-2 diminished progressively f rom proliferative phase and hyperplastic endometrium to UEC and then t o UPSC, with 3 of 21 (14.3%) UPSC being negative. These results sugges t that p53 alteration may be an early event in the development of UPSC and may be related to its clinical aggressiveness, while it is a late event in UEC. Early detection of p53 nuclear accumulation may help to identify precursor lesions of UPSC. bcl-2 persistence is frequently a ssociated with endometrial carcinoma, and failure to inactivate bcl-2 expression probably is related to the development of endometrial carci noma. (C) 1996 Academic Press, Inc.