ALPHA-SUBUNIT AND BETA-SUBUNIT OF INHIBIN ACTIVIN AS SEX CORD-STROMALDIFFERENTIATION MARKERS/

Inhibins (alpha and beta heterodimers) and activins (beta homodimers) are related peptides with opposing biologic action on gonadotropin reg ulation. They serve as components of the pituitary-gonadal feedback sy stem. Although sex-cord stromal tumors can usually be distinguished fr om ovarian epithelial tumors or their metastases by morphology or by u sing antibodies against intermediate filaments, the diagnosis remains difficult in rare situations in such cases as sarcomatoid granulosa-th eca cell tumors, ovarian small cell carcinomas, or soft-tissue sarcoma s. A total of 28 sex cord-stromal tumors of the ovary and 43 non-sex c ord-stromal tumors were immunohistochemically evaluated for the presen ce of alpha and beta subunits of inhibin and activin. For comparison, 10 normal adult gonads including seven ovaries with hilar regions and three testes also were examined. Immunoreactivity for both alpha and b eta subunits of inhibin/activin was identified in both non-neoplastic and neoplastic granulosa, Sertoli, Leydig, hilar and luteinized theca cells, with the strongest immunoreactivity in Leydig and hilar cells. One of three Sertoli-Leydig cell tumors that showed a sarcomatoid grow th pattern and one sex-cord tumor with annular tubules also were immun oreactive for both subunits. For non-sex cord stromel-derived ovarian tumors, a subunit immunoreactivity was negative in al but two of five ovarian mucinous tumors. Weak immunoreactivity for beta subunit was fo und in most ovarian surface epithelial carcinomas, two of four colonic , and one of three pancreatic carcinomas. No immunostaining was found in nonspecialized gonadal stromal or interstitial cells, thecal cells, germ cells, ovarian small cell carcinomas, carcinoid tumors, dysgermi nomas, or leiomyosarcomas. Immunostaining of alpha subunit (inhibin al pha), but not of beta subunit could serve as a sex cord-stromal differ entiation marker because ct subunit alone is largely confined to sex c ord-stromal lesions with the exception of some ovarian mucinous tumors . Further studies are needed to define the usefulness of this sex cord -stromal differentiation marker in the practice of surgical pathology. Coexpression of alpha and beta subunits in sex cord-stromal elements suggests that dimeric inhibin is expressed in these cells.