Cleaved caspase-3 and nuclear factor-kappaB p65 are prognostic factors in metastatic serous ovarian carcinoma.
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.
Kleinberg
Lilach
L
Norwegian Radium Hospital, Rikshospitalet Medical Center, Oslo, Norway.
Dong
Hiep Phuc
HP
Holth
Arild
A
Risberg
Björn
B
Trope'
Claes G
CG
Nesland
Jahn M
JM
Flørenes
Vivi Ann
VA
Davidson
Ben
B
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*
D003856:Deoxyuracil Nucleotides; D051996:Transcription Factor RelA; C027078:deoxyuridine triphosphate; D053148:Caspase 3; D053181:Caspase 8