Expression of Müllerian Inhibiting Substance, CD99 and HEA125 in Ovarian Tumors

Abstract

Objective: The expression of Mullerian inhibiting substance (MIS), CD99 (MIC-2 gene product), and HEA125 in ovarian tumors is potentially useful for diagnostic purposes. Methods: We studied the expression of MIS, CD99, and an epithelial cell-associated antigen recognized by antibody HEA125 in a series of 179 ovarian tumors using monoclonal or polyclonal antibodies and standard immunohistochemical techniques. Results: MIS was consistently detected in primary and metastatic sex cord tumors with annular tubules (SCTAT) (n = 9). 3 of 9 adult granulosa cell tumors (AGCT), 4 of 8 juvenile granulosa cell tumors (JGCT), 3 of 9 Sertoli cell tumors (SCT), 2 of 2 unclassified sex cord tumors, 2 of 7 steroid cell tumors, 1 of 1 gonadoblastoma (sex cord cells positive, germ cells negative), 3 of 8 female adnexal tumors of probable wolffian origin (FATPWO), and 2 of 4 small cell carcinomas of the hypercalcemic type (SCCHCT) were also MIS positive. In contrast, 9 thecomas, 10 fibromas, 10 fibrosarcomas, 8 sclerosing stromal tumors (SST), and 6 Sertoli-Leydig cell tumors (SLCT) were MIS negative. All 11 primary and metastatic JGCT were CD99 positive. In addition, 4 of 13 AGCTs, 3 of 11 thecomas, 3 of 11 SSTs, 3 of 11 SCTs, 2 of 10 SLCTs, 2 of 12 SCTATs, 1 of 1 gynandroblastoma, 1 of 2 unclassified sex cord tumors, and 4 of 12 SCCHCTs were also CD99 positive. However, 11 fibromas, 10 fibrosarcomas, 9 steroid cell tumors, 5 gonadoblastomas, and 10 FATPWOs were CD99 negative. Likewise, except for weak focal CD99 immunostaining in 1 of 3 yolk sac tumors (YST), all 16 remaining germ cell tumors and all 18 borderline or malignant epithelial-stromal tumors were negative. HEA125 immunoreactivity was detected in 2 of 11 thecomas, 1 of 11 SCTs, 4 of 10 SLCTs, of 2 unclassified sex cord tumors, 1 of 10 FATPWOs, 4 of 12 SCCHCTs as well as in most germ cell tumors and epithelial-stromal tumors. 13 AGCTs, 11 JGCTs, 11 fibromas, 10 fibrosarcomas, 11 SSTs, 12 SCTATs, 1 gynandroblastoma, 9 steroid cell tumors, and 5 gonadoblastomas were HEA125 negative. Conclusion: Our findings indicate that MIS is a maker of sexcord differentiation and may be useful as a serum tumor marker for certain sex cord tumors, especially SCTAT. Although the detection of MIS and CD99 in some SCCHCTs and FATPWOw might argue in favor of a sex cord origin, the histogenesis of these tumors remains unclear. Although inhibin-α has previously been shown to be immunohistochemical markers including MIS, CD99 and HEAT125 may be hepful in the differential diagnosis of certain ovarian neoplasms.