IMBALANCED EXPRESSION OF INHIBIN AND ACTIVIN SUBUNITS IN PRIMARY EPITHELIAL OVARIAN-CANCER

Objectives. Inhibins and activins are related gonadal peptides with op posing biologic actions on gonadotropin regulation, cell differentiati on, and proliferation, The previous study of activin in ovarian cancer cell lines suggests that activin may promote growth of ovarian cancer . Elevated serum inhibin levels were also found in ovarian cancer pati ents; however, the source of elevated inhibin is unknown. This study i s designed to examine the expression of inhibin and activin subunits a s well as activin receptor in primary ovarian epithelial tumors to exp lore their role in the process of ovarian epithelial tumorigenesis. Me thods. The protein and mRNA expression of alpha and beta A subunits of inhibin/activin as well as of activin receptor mRNA were examined wit h immunohistochemistry (IHC) and reverse transcription-polymerase chai n reaction (RT-PCR) in 112 ovarian carcinomas, Cases included 59 serou s, 23 endometrioid, 16 mucinous, 9 clear cell, and 5 undifferentiated carcinomas. We also tested normal ovary and benign and borderline ovar ian tumors for comparison. These included 17 ovarian surface epithelia l samples, 6 serous and 5 mucinous cystadenomas, and 9 serous and 7 mu cinous tumors of low malignant potential. A total of 139 ovarian tumor s were analyzed by IHC and a total of 63 ovarian tumor samples were te sted by RT-PCR. Results. Inhibin alpha subunit expression was found in 47% of ovarian surface epithelia and focal alpha immunoreactivity was seen in tumor stroma, but was not found in the epithelial component o f ovarian cystadenomas, tumors of low malignant potential (LMP), or ca rcinomas, Activin beta A subunit was expressed in 93% of surface epith elia, in the epithelial component of all cystadenomas, in 81% of LMP t umors, and in 72% of carcinomas, but not in tumor stroma, Activin expr ession did not correlate with histologic grades, tumor types, and surg ical stages, Activin receptor type I and II mRNA-amplified products we re found in virtually all the surface epithelial samples and ovarian t umors. Conclusions. The data suggest that imbalanced expression of inh ibin and activin subunits in ovarian surface epithelium may represent an early event which leads to epithelial proliferation. Unopposed beta A and activin receptor expression in epithelial compartment of ovaria n tumors suggest that activin may be available as autocrine and/or par acrine factors in ovarian epithelial tumors. But exact roles of inhibi n and activin in ovarian epithelial tumors remain to be defined. (C) 1 998 Academic Press.