Utility of FISH in the Molecular Diagnosis of Ovarian Germ Cell Tumors
Alejandro A Gru, Andrea L Salavaggione, Julie Branson, Diane Robirds, Phyllis C Huettner, Dengfeng Cao. Washington University in St. Louis School of Medicine, Saint Louis, MO
Background: Malignant ovarian germ cell tumors (GCT) are uncommon neoplasms that can be diagnostically challenging, and are important in the differential diagnosis of a variety of tumors. Little is known about their molecular pathogenesis. Fluorescent in-situ hybridization (FISH) has been proven to be useful as a molecular tool for the diagnosis of testicular GCT, and the presence of isochromosome 12 (i(12p)) has been demonstrated in dysgerminoma, the most common malignant ovarian GCT.
Design: Cases of primary ovarian GCT were retrieved: 59 cases, including 4 gonadoblastomas (GNB), 2 embryonal carcinomas (EC), 6 immature teratomas (IT), 2 struma ovarii (SO), 21 yolk sac tumors (YST) and 24 dysgerminomas (DYS), were obtained. Interphase FISH was performed on formalin-fixed paraffin embedded tissue as previously described, using the following probes: spectrum orange centromeric (CEP) 12, spectrum green subtelomeric (Tel12p), spectrum orange CEP 9, and spectrum acqua CEP X (Vysis, Abbott Molecular). We also used a homemade probe for the DMRT1 gene.
Results: FISH detected several chromosomal abnormalities: all cases of GNB, SO, and the majority of IT lacked i(12p) or 12p overrepresentation. Monosomy X was seen in 50% of GNB and 20% of IT. Polysomy X and 9 was seen in 25% of GNB and 33% of IT. YST had i(12p) or 12p overrepresentation in 28% of cases. 30% had polysomy X and 15% monosomy X. 15% showed either polysomy or monosomy 9. Among DYS, 59% showed 12p overrepresentation (fig.1a) and 29% had i(12p). 27% had either monosomy or polysomy X. 18% showed polysomy 9 and 9% monosomy 9. Two cases (1 YST and 1 DYS) showed DMRT1 deletion (fig.1b). In the 2 cases of EC, one show numerical chromosomal gains, and the other was normal. The 2 cases of SO had normal cytogenetic findings. 12p overrepresentation was more common in YST and DYS, compared to GNB, SO and IT (50% vs 9%, p=0.02). 52% of GCT showed numerical changes of chromosomes X and 9, and DMRT1 amplification was not present.
Conclusions: Contrary to the preexisting evidence, i(12p) or 12p overrepresentation has a relatively low sensitivity (59%) for dysgerminoma diagnosis but a good specificity (83%). Numerical changes in chromosomes X and 9 are very frequent in ovarian GCTs and may be important in their pathogenesis.
Category: Gynecologic & Obstetrics
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 190, Monday Morning