The Sertoli Cell Associated Molecule Doublesex and Mab-3 Related Transcription Factor 1 (DMRT-1) Is Not Expressed in Sertoli-Leydig Cell Tumors of the Ovary.
Rebecca Buell-Gutbrod, Anthony Montag, Oluwole Fadare, Ernst Lengyel, Katja Gwin. University of Chicago, IL; Vanderbilt University, Nashville
Background: Sertoli-Leydig cell tumors (SLCTs) of the ovary are composed of sex-cord derivatives resembling those of the testis and a stromal component containing variable amounts of Leydig cells. Based on morphology the sex-cord cells have traditionally been regarded as Sertoli cells. However, true Sertoli cells are not present in the adult female gonad and the origin of these cells is unclear. Doublesex and mab-3 related transcription factor 1 (DMRT1) is a key regulator of male development and is expressed in Sertoli cells of the developing and adult male gonad. Mutations in the DMRT1 gene result in defective testicular development and XY feminization.
Design: Archival paraffin embedded material of 10 SLCTs, 3 Leydig cell tumors, one Sertoli cell (SC) hamartoma arising in a background of testicular feminization, a TMA containing 38 granulosa cell tumors (GCTs), and normal ovarian and testicular tissue as controls, were examined by IHC for the expression and localization of DMRT-1.
Results: The sex cord-stromal derivatives of the SLCTs revealed no expression (0/10) of DMRT1. Two cases showed weak cytoplasmic staining in the Leydig cell component. Two cases of Leydig cell tumors were negative for DMRT1 expression, with weak cytoplasmic staining in one case. All 38 GCTs were devoid of DMRT1 expression. The Sertoli cell hamartoma showed moderate (2+) nuclear expression. Sertoli cells in adult testis showed moderate to strong nuclear expression while no expression was seen in the granulosa cells of normal adult ovaries.
Conclusions: DMRT1 is a transcription factor with a Zinc finger-like DNA-binding motif (DM domain) that is a highly conserved component of the male vertebrate sex-determining pathway. Its expression has been demonstrated in Sertoli cells of the testis by ISH in the past. We show that it is also expressed by IHC in Sertoli cells of adult testes and in Sertoli cell hamartomas, but is not seen in so called Sertoli-Leydig cell tumors of the ovary nor is it seen in GCTs or normal granulosa cells of the ovary. This suggests that the sex-cord derivatives of SLCTs are not of Sertoli cell lineage but may be of granulosa cell lineage.
Category: Gynecologic & Obstetrics
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 123, Tuesday Afternoon