title: Ovarian carcinoma cells in effusions show increased S-phase fraction compared to corresponding primary tumors.
abstract: The objective of this study was to analyze large-scale genomic patterns during disease progression from primary tumor to effusion in ovarian carcinoma, and to study the association between DNA ploidy parameters in effusions, proliferation/survival markers, and clinicopathologic characteristics. DNA ploidy status, DNA index (DI), and S-phase fraction (SPF) were compared in 22 matched primary carcinomas (all prechemotherapy specimens) and effusions (14 prechemotherapy and 8 postchemotherapy specimens) using image analysis. The association between these parameters and previously studied cell survival/proliferation biomarkers, previous administration of chemotherapy, chemotherapy response and survival was analyzed in a larger series of 54 effusions. The majority of specimens were aneuploid irrespective of anatomic site, with no significant differences in DI. SPF was significantly higher in effusions compared to matched primary tumors (P = 0.007 for all 22 pairs, P = 0.011 for 14 matched prechemotherapy specimens). Higher SPF was related to higher Ki-67 score (P = 0.045), and both SPF and DI were directly associated with higher level of Survivin (P < 0.001 for both). DI and SPF in effusions showed no association with histological grade, FIGO stage, residual disease volume, previous chemotherapy, response to chemotherapy at primary disease, recurrence or survival. Ovarian carcinoma cells in effusions have increased proliferation compared to corresponding primary tumors, as evidence of disease progression. DNA ploidy parameters in cancer cells in effusions are unaltered by chemotherapy and appear to be unrelated to chemotherapy response and to survival, suggesting that large-scale genomic patterns at this anatomic site are not useful in segregating patients into prognostic groups.
authors.affiliation: Division of Pathology, The Norwegian Radium Hospital, Rikshospitalet Medical Center, Oslo, Norway.
authors.forename: Lilach
authors.initials: L
authors.lastname: Kleinberg
authors.forename: Manohar
authors.initials: M
authors.lastname: Pradhan
authors.forename: Claes G
authors.initials: CG
authors.lastname: Tropé
authors.forename: Jahn M
authors.initials: JM
authors.lastname: Nesland
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
authors.forename: Björn
authors.initials: B
authors.lastname: Risberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation; D004273:DNA, Neoplasm / Q000032:analysis; D004171:Diploidy; D005122:Exudates and Transudates / Q000166:cytology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology*; D016196:S Phase; D013347:Subcellular Fractions / Q000473:pathology; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm