title: Evaluation of genomic changes in a large series of malignant ovarian germ cell tumors--relation to clinicopathologic variables.
abstract: Malignant ovarian germ cell tumors (mOGCT) affect women in their reproductive years, making fertility-saving treatment important. A reliable prediction of the clinical behavior is essential for an optimal therapeutic approach. The genetic changes and molecular mechanisms underlying these rare tumors remain poorly understood. To address these issues, we performed DNA ploidy analysis by high-resolution image cytometry in a series of 47 mOGCT and correlated the findings with the DNA copy number changes detected by comparative genomic hybridization (CGH) and clinical outcome. Of 47 tumors, 15 were diploid, 14 were tetraploid, 2 were polyploid, and 13 were aneuploid. All the immature teratomas were diploid, in contrast to the dysgerminomas and endodermal sinus tumors. The International Federation of Gynecology and Obstetrics (FIGO) staging, residual tumors after surgery, and DNA ploidy distribution were significant, independent prognostic factors in survival analysis. The study revealed that the number of DNA copy number aberrations was increased in tetraploid and aneuploid tumors as compared to diploid tumors. Furthermore, a high percentage of aneuploid nuclei in a sample were associated with a complex CGH profile of the tumor in question. The present study confirms that DNA aneuploidy assessment by image analysis may be linked to genetic instability, which is detected as genetic aberrations by CGH. DNA ploidy gives significant prognostic information in addition to the clinical stage in mOGCT with FIGO stage II-IV.
authors.affiliation: Department of Pathology, Institute for Cancer Research, The University Clinic of the Norwegian Radium Hospital, Oslo, Norway. wanjak@labmed.uio.no
authors.forename: Wanja
authors.initials: W
authors.lastname: Kildal
authors.forename: Janne
authors.initials: J
authors.lastname: Kaern
authors.forename: Sigrid Marie
authors.initials: SM
authors.lastname: Kraggerud
authors.forename: Vera M
authors.initials: VM
authors.lastname: Abeler
authors.forename: Jon
authors.initials: J
authors.lastname: Sudbø
authors.forename: Claes G
authors.initials: CG
authors.lastname: Tropè
authors.forename: Ragnhild A
authors.initials: RA
authors.lastname: Lothe
authors.forename: Håvard E
authors.initials: HE
authors.lastname: Danielsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000782:Aneuploidy; D002467:Cell Nucleus / Q000378:metabolism; D002648:Child; D004247:DNA / Q000032:analysis / Q000235:genetics; D004171:Diploidy; D005260:Female; D018237:Germinoma / Q000235:genetics*; D006801:Humans; D019044:Image Cytometry / Q000379:methods; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D010051:Ovarian Neoplasms / Q000235:genetics*; D011003:Ploidies; D011123:Polyploidy; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D004247:DNA