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: Lilach Kleinberg, Hiep Phuc Dong, Arild Holth, Björn Risberg, Claes G Trope', Jahn M Nesland, Vivi Ann Flørenes, Ben Davidson (Affiliation: Norwegian Radium Hospital, Rikshospitalet Medical Center, Oslo, Norway.)
• Journal: Human pathology (Hum Pathol) Vol. 40 Issue 6 Pg. 795-806 (Jun 2009) ISSN: 1532-8392 [Electronic] United States
• PMID: 19157506 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Deoxyuracil Nucleotides
• Transcription Factor RelA
• deoxyuridine triphosphate
• Caspase 3
• Caspase 8

Topics

• Adult
• Aged
• Aged, 80 and over
• Apoptosis
• Caspase 3 (genetics)
• Caspase 8 (genetics)
• Cystadenocarcinoma, Serous (genetics, pathology)
• Deoxyuracil Nucleotides (metabolism)
• Female
• Flow Cytometry
• Humans
• Middle Aged
• Ovarian Neoplasms (genetics, pathology)
• Pleural Effusion, Malignant (etiology, pathology)
• Prognosis
• Transcription Factor RelA (genetics)