Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
4134519 | Human Pathology | 2009 | 12 Pages |
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-κB p65, nuclear factor-κB inhibitor α, 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-κB p65 and nuclear factor-κB inhibitor α expression. Effusions (n = 75) were further analyzed for nuclear factor-κB 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-κB p65 expression was frequently detected at all anatomic sites, with less frequent cytoplasmic nuclear factor-κB p65 and nuclear factor-κB inhibitor α expressions. Immunoblotting showed nuclear factor-κB 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-κB 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-κB p65 is frequently expressed in advanced-stage serous ovarian carcinoma, and its nuclear localization is associated with poor progression-free survival.
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Authors
Lilach MSc, Hiep Phuc MSc, Arild BSc, Björn MD, PhD, Claes G. MD, PhD, Jahn M. MD, PhD, Vivi Ann PhD, Ben MD, PhD,