Use of monoclonal antibody against human inhibin as a marker for sex cord-stromal tumors of the ovary.

Abstract

Inhibin is a glycoprotein hormone produced by normal ovarian granulosa cells and testicular sertoli cells. In the ovary, it inhibits the secretion of follicle-stimulating hormone. Patients with granulosa cell tumors (GCT) have elevated serum levels of inhibin and this finding has been used to detect recurrent tumor. This study attempts to determine whether inhibin antibody (IAB) can preferentially mark GCT and Sertoli-cell or Sertoli-Leydig cell tumors (SCT) in paraffin-embedded tissues and facilitate distinction of GCT from small cell carcinoma of hypercalcemic type (SCC), SCT from Sertoliform endometrioid carcinoma (SEC), and primitive gonadal-stromal tumors from a variety of poorly differentiated neoplasms. Applying microwave-enhanced immunohistochemistry, a total of 126 paraffin-embedded and microwave-enhanced archival ovarian tumors and tissues were studied by using monoclonal IAB. The tumors included 32 adult GCT, 7 juvenile GCT, 4 metastatic GCT, 8 SCT, 7 SCC, 6 primitive gonadal stromal tumors (PGST), 5 fibrothecomas, 6 lipid cell tumors (LCT), 5 extrauterine endometrial stromal sarcomas (ESS), 5 hemangiopericytomas (HPC), 1 metastatic malignant melanoma, 1 metastatic malignant lymphoma, and 27 epithelial tumors including 8 SEC, 5 mucinous tumors, and 4 Brenner tumors. Seven pregnancy luteomas (nodular theca lutein hyperplasia of pregnancy), 3 corpora lutea and 2 ovarian follicles were also studied. The intensity of immunostaining was scored from one to three and the percentage of the immunoreactive tumor cells was determined and expressed in 10% increments. Among 32 adult GCT, 31 (97%) tumors reacted positively with IAB. The percent of positive cells ranged from 30% to 100% (average 80%). Similarly, all four metastatic GCT, 7 juvenile GCT and 4 of 5 fibrothecomas were immunoreactive with monoclonal IAB. Seven of 8 (88%) SCT, 5 of 6 (83%) PGST, all 6 LCT, 7 pregnancy luteomas, 3 corpora lutea and the 2 ovarian follicles were also positive with IAB. The most intense positivity was observed in luteinized stromal cells regardless of tumor type. No immunoreactivity was observed in any of the 7 SCC, 5 ESS, 5 HPC, 1 metastatic malignant melanoma, 1 metastatic malignant lymphoma and the epithelial component of all 27 epithelial tumors including 8 SEC. Among the mucinous tumors of the ovary, however, 3 tumors with luteinized stromal cells showed immunoreactivity in these cells, but no positivity was seen in the mucinous epithelium. We conclude that IAB is an excellent marker for sex cord differentiation in ovarian tumors. It can be used effectively in the diagnosis of GCT and its distinction from epithelial neoplasms particularly SCC. The IAB may also be helpful in differentiating LCT from epithelial malignancies. However, it cannot be used to distinguish GCT from SCT.