Inhibin and activin: Their roles in ovarian tumorigenesis and their diagnostic utility in surgical pathology practice

Bioactive inhibins (α plus β subunit) and activins (two β subunits) are related nonsteroidal dimeric proteins by virtue of their sharing two common β subunits. Initially, both inhibin and activin were believed to act exclusively as endocrine nonsteroid hormones. It soon became apparent that inhibin and activin subunits were expressed in a wide variety of gonadal and nongonadal tissues, suggesting that these peptides have other functions in addition to regulating follicle-stimulating hormone (FSH) secretion. Recently, inhibin α has been proposed to be a sex cord-stromal differentiation marker, and much interest has arisen regarding the roles of inhibin and activin in the pathogenesis and diagnosis of both ovarian epithelial and sex cord-stromal tumors (SCSTs). In this article, we briefly review the structure of bioactive inhibin and activin and their tissue distribution. We present the current opinion regarding the function of both inhibin and activin in the development of ovarian tumors. The important progress in the field is summarized. Considerable interest in the topic of inhibin has grown in the fields of surgical pathology and immunohistochemistry. After inhibin α was first reported as an immunohistochemical marker of granulosa cell tumors in 1995, many reports regarding the use of inhibin α as a sensitive diagnostic marker for gonadal SCSTs have been published. There is a need for a summary of current opinion for, among others, surgical pathologists, both in training and in practice. In general, immunohistochemical staining of inhibin α proves to be a valuable diagnostic marker for ovarian SCSTs, but caution should be paid in certain situations for the low specificity of inhibin tissue expression. The usefulness of inhibin α immunostaining in the diagnosis of ovarian SCSTs is summarized. The indications and limitations are also discussed.