AROMATASE IN HUMAN ENDOMETRIAL CARCINOMA AND HYPERPLASIA - IMMUNOHISTOCHEMICAL, IN-SITU HYBRIDIZATION, AND BIOCHEMICAL-STUDIES

The expression of P450 aromatase and other steroidogenic enzymes were evaluated in 42 endometrioid endometrial carcinomas, 23 endometrial hy perplasias, and 7 normal endometrial specimens. These findings were co rrelated with clinicopathological findings to elucidate the possible b iological significance of in situ estrogen production in the developme nt of human endometrial carcinoma. Only weak aromatase immunoreactivit y was observed in vascular walls and myometrial cells. In contrast, st rong aromatase stromal immunoreactivity, was observed in 28 of 42 (66. 7%) endometrial carcinomas. However, no stromal immunoreactivity was s een in normal or hyperplastic endometrial specimens. Immunoreactivity in the carcinoma stromal cells was significantly increased at sites of invasion, These aromatase-positive cells were immunohistochemically n egative for other steroidogenic enzymes involved in estrogen biosynthe sis. In situ hybridization studies revealed aromatase mRNA hybridizati on signals in stromal cells but not in carcinoma cells. The distributi on of aromatase mRNA correlated well with the immunohistochemical loca lization of aromatase enzyme. Quantitation of aromatase activity demon strated 8.75 +/- 2.75 pmol/hour/mg of protein for endometrial carcinom as (22 specimens) and 0.98 +/- 1.95 pmol/hour/mg of protein for normal endometrial specimens (4 specimens). Aromatase activity was found in both estrogen receptor-positive and -negative endometrial carcinomas. Aromatase did not vary with respect to the menopausal status of patien ts with endometrial carcinoma. These results suggest that estrogen is produced in situ in endometrial carcinoma but not in benign endometria l lesions. Such locally synthesized estrogen may act on carcinoma cell s in a paracrine fashion to promote tumor growth. Additional investiga tions are necessary, but increased aromatase expression in the stromal cells of endometrial carcinoma may therefore play an important role i n the development of human endometrioid endometrial carcinoma.