CLEAR-CELL CARCINOMA OF THE ENDOMETRIUM IS CHARACTERIZED BY A DISTINCTIVE PROFILE OF P53, KI-67, ESTROGEN, AND PROGESTERONE-RECEPTOR EXPRESSION

This study was designed to analyze certain clinicopathological feature s and the profile of p53, Ki-67, estrogen (ER), and progesterone (PR) receptor expression of clear fell carcinoma of the endometrium and to determine whether the pathogenesis of clear cell carcinoma can be acco mmodated by a dualistic model of endometrial carcinogenesis. In this m odel, endometrioid carcinoma develops from endometrial hyperplasia und er unopposed estrogenic stimulation, and serous carcinoma develops in atrophic endometrium from a putative precursor lesion designated endom etrial intraepithelial carcinoma (EIC). Twenty-one clear cell carcinom as of the endometrium were analyzed and compared with 77 endometrioid carcinomas of all grades and 30 serous carcinomas. Clear cell carcinom as showed a distinctive immunoprofile characterized by immunonegativit y for ER and PR, low immunoreactivity for p53, and a high Ki-67 prolif eration index. ER, PR, and Ki-67 expression were similar to serous car cinoma, but p53 expression was significantly lower in clear cell carci noma (P < .05). ER and PR expression were significantly lower, and the Ki-67 proliferation index was significantly higher in clear cell carc inoma compared with endometrioid carcinomas (P < .05). p53 expression tended to be higher in clear cell carcinoma compared with endometrioid carcinoma, but the difference was not statistically significant. In c ontrast to endometrioid carcinoma, clear cell carcinoma was rarely ass ociated with endometrial hyperplasia and serous carcinoma was not. Sub dividing clear fell carcinoma morphologically into one that resembled serous carcinoma (clear cell carcinoma with serous features) and anoth er that did not (typical clear cell carcinoma) showed that clear cell carcinoma with serous features had a higher Ki-67 proliferation index than typical clear cell carcinoma, although expression of ER, PR, and p53 were similar. Clear cell carcinoma with serous features was associ ated with EIC in 50% and was not associated with endometrial hyperplas ia. In contrast, typical clear cell carcinoma was associated with endo metrial hyperplasia in 40% and was not associated with EIC. In summary , this study provides evidence that clear cell carcinoma of the endome trium, like serous carcinoma, is estrogen independent and shows a high Ki-67 proliferation index. In contrast to serous carcinoma, strong p5 3 expression occurred less frequently in clear cell carcinoma and pred ominantly in clear cell carcinoma with serous features. The findings s uggest that the molecular events that underlie the development of clea r cell carcinoma differ from those of endometrioid and serous carcinom a. HUM PATHOL 29:551-558. Copyright (C) 1998 by W.B. Saunders Company.