title: Cleaved caspase-3 and nuclear factor-kappaB p65 are prognostic factors in metastatic serous ovarian carcinoma.
abstract: Tumor progression and treatment failure in ovarian carcinoma are frequently associated with metastasis to effusions. The present study analyzed the expression and clinical role of nuclear factor-kappaB p65, nuclear factor-kappaB inhibitor alpha, and parameters of apoptosis in serous carcinoma. Cleaved caspase-3 and caspase-8 levels and deoxyuridine triphosphate incorporation were measured in 65 effusions using flow cytometry. Effusions (n = 209) and corresponding primary carcinomas and solid metastases (n = 114) were immunohistochemically analyzed for nuclear factor-kappaB p65 and nuclear factor-kappaB inhibitor alpha expression. Effusions (n = 75) were further analyzed for nuclear factor-kappaB phospho-p65 (Ser536) levels using immunoblotting. Results were analyzed for association with anatomic site, clinicopathologic parameters, and survival. Caspase cleavage and deoxyuridine triphosphate incorporation were limited to less than 10% of cells in most effusions. Nuclear factor-kappaB p65 expression was frequently detected at all anatomic sites, with less frequent cytoplasmic nuclear factor-kappaB p65 and nuclear factor-kappaB inhibitor alpha expressions. Immunoblotting showed nuclear factor-kappaB p65 phosphorylation in 72 (96%) of 75 effusions. Higher than median cleaved caspase-3 levels correlated with improved overall and progression-free survival in univariate analysis of all patients (P = .024 and P = .046, respectively) and of those with postchemotherapy effusions (P = .042 and P = .036, respectively). Cleaved caspase-3 expression was an independent predictor of longer progression-free survival for patients with postchemotherapy effusions (P = .029). Nuclear factor-kappaB p65 expression correlated with poor progression-free survival for all patients (P = .048) and for those with postchemotherapy effusions (P = .025). Ovarian carcinoma cells in effusions undergo little apoptosis, but high levels of cleaved caspase-3 are associated with improved survival. Nuclear factor-kappaB p65 is frequently expressed in advanced-stage serous ovarian carcinoma, and its nuclear localization is associated with poor progression-free survival.
authors.affiliation: Norwegian Radium Hospital, Rikshospitalet Medical Center, Oslo, Norway.
authors.forename: Lilach
authors.initials: L
authors.lastname: Kleinberg
authors.forename: Hiep Phuc
authors.initials: HP
authors.lastname: Dong
authors.forename: Arild
authors.initials: A
authors.lastname: Holth
authors.forename: Björn
authors.initials: B
authors.lastname: Risberg
authors.forename: Claes G
authors.initials: CG
authors.lastname: Trope'
authors.forename: Jahn M
authors.initials: JM
authors.lastname: Nesland
authors.forename: Vivi Ann
authors.initials: VA
authors.lastname: Flørenes
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D053148:Caspase 3 / Q000235:genetics*; D053181:Caspase 8 / Q000235:genetics; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000473:pathology*; D003856:Deoxyuracil Nucleotides / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D016066:Pleural Effusion, Malignant / Q000209:etiology* / Q000473:pathology; D011379:Prognosis; D051996:Transcription Factor RelA / Q000235:genetics*
chemical_list: D003856:Deoxyuracil Nucleotides; D051996:Transcription Factor RelA; C027078:deoxyuridine triphosphate; D053148:Caspase 3; D053181:Caspase 8