title: Characteristic pattern of genetic aberrations in ovarian granulosa cell tumors.
abstract: The cytogenetic abnormalities of granulosa cell tumors (GCT) of the ovary are only partially known. Up to now, mainly numerical chromosomal aberrations have been described. Therefore we performed a comprehensive study on paraffin-embedded material of 20 GCT (17 adult, 3 juvenile; patient age between 16 and 78 y) combining comparative genomic hybridization (CGH); fluorescence in situ hybridization (FISH) using DNA-specific probes for chromosome 12, 17, 22, and X; DNA cytometry; and immunohistochemistry (inhibin, p53, Ki67). By DNA cytometry, 16 of 20 tumors (80%) were diploid. However, 6 of 16 diploid tumors (37%) showed aberrations by FISH. FISH revealed monosomy 22 in 8/18 cases (40%); trisomy 12 in 5/20 (25%); monosomy X in 2/20 (10%); and loss of chromosome 17 in one case (5%). The main findings by CGH were gains of chromosomes 12 (6 cases, 33%) and 14 (6 cases, 33%) and losses of chromosomes 22 (7 cases, 35%) and X (1 case, 5%), mostly comprising whole chromosomes or chromosome arms. Inhibin and p53 were expressed in 100% and 95% of the tumors, respectively. The Ki67 index ranged from 0% to 61%. Neither immunohistochemistry, nor DNA cytometry and molecular genetic analysis, provided statistically significant prognostic information. In summary, our study reveals a distinctive pattern of cytogenetic alterations in GCT. Our observations confirm earlier reports that trisomy 12 and 14 are frequent aberrations; however, monosomy 22 seemingly is even more prevalent.
authors.affiliation: Pathological Institute, University of Munich, Munich, Germany. doris.mayr@lrz.uni-muenchen.de
authors.forename: D
authors.initials: D
authors.lastname: Mayr
authors.forename: C
authors.initials: C
authors.lastname: Kaltz-Wittmer
authors.forename: S
authors.initials: S
authors.lastname: Arbogast
authors.forename: G
authors.initials: G
authors.lastname: Amann
authors.forename: D E
authors.initials: DE
authors.lastname: Aust
authors.forename: J
authors.initials: J
authors.lastname: Diebold
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D006106:Granulosa Cell Tumor / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D006801:Humans; D019044:Image Cytometry; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007265:Inhibins / Q000096:biosynthesis; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D007265:Inhibins