title: Analysis of gene amplification and prognostic markers in ovarian cancer using comparative genomic hybridization for microarrays and immunohistochemical analysis for tissue microarrays.
abstract: To identify oncogene amplification involved in ovarian carcinogenesis, we studied 21 ovarian carcinomas and 5 serous borderline tumors using conventional comparative genomic hybridization (CGH) and CGH to a genomic DNA microarray. Immunohistochemical analysis of the proteins encoded by the genes that were amplified frequently (FGF3/4, FGFR1, CCNE1, PAK1, JUNB, and MDM2) was performed on a tissue microarray comprising 254 cases of ovarian neoplasms. Regarding histologic type, characteristic patterns of copy number changes were revealed. They correlated with histologic tumor type and with intratumoral heterogeneity. Gain of FGF3/4 and CCNE1 was found in all serous carcinomas. Endometrioid carcinomas most frequently showed gain of JUNB (83%), KRAS2 (67%), MYCN (50%), ESR (50%), and CCND2 (50%). Of the serous borderline tumors, 80% harbored amplification of FGFR1 and MDM2 and a 75% gain of PIK3CA. Only CCNE1 immunoreactivity was significantly correlated with CGH results (P < .05) and postoperative survival (P < .05). Microarray-based genomic analysis in combination with immunohistochemical analysis was found to be a powerful technique for identification of clinically relevant gene amplification in human ovarian cancer.
authors.affiliation: Institute of Pathology, Ludwig-Maximilians University Munich, Munich, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Mayr
authors.forename: Veronika
authors.initials: V
authors.lastname: Kanitz
authors.forename: Birgit
authors.initials: B
authors.lastname: Anderegg
authors.forename: Beate
authors.initials: B
authors.lastname: Luthardt
authors.forename: Jutta
authors.initials: J
authors.lastname: Engel
authors.forename: Udo
authors.initials: U
authors.lastname: Löhrs
authors.forename: Gudrun
authors.initials: G
authors.lastname: Amann
authors.forename: Joachim
authors.initials: J
authors.lastname: Diebold
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D046888:Tissue Array Analysis / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm