Nuclear overexpression of mitotic regulatory proteins in biliary tract cancer: Correlation with clinicopathologic features and patient survival
Journal
Cancer Epidemiology Biomarkers and Prevention
Journal Volume
18
Journal Issue
2
Pages
417-423
Date Issued
2009
Author(s)
Abstract
Mitosis dysregulation is common in cancers. This study explored the nuclear expression patterns and prognostic significance of mitotic regulatoryproteins, including Aurora kinases, survivin, and p53, in biliarytract cancer (BTC). Archival tumor samples from 161 BTC patients who underwent surgerywere tested for the expression of Aurora-A, Aurora-B, survivin, and p53 by immunohistochemistry. The potential endogeneity among the clinicopathologic variables and survival outcome was assessed by a generalized simultaneous equations model. Nuclear overexpression of Aurora-A, Aurora-B, survivin, and p53 was found in 79 (49.1%), 45 (28.0%), 55 (34.2%), and 55 (34.2%) patients, respectively. Intrahepatic cholangiocarcinoma, compared with the other two subtypes, had significantly higher proportions of nuclear overexpression of Aurora-B and survivin (37.8% and 47.3%, respectively). Simultaneous overexpression of Aurora-A and Aurora-B was correlated with that of p53. Overexpression of Aurora-B was also correlated with that of survivin and tumor grade. Our data indicate that simultaneous overexpression of Aurora-A and Aurora-B, suggesting dysregulated mitosis is associated with worse survival in patients with BTC. Independent prognostic factors for poor overall survival included simultaneous overexpression of Aurora-A and Aurora-B (hazard ratio, 1.997; 95% confidence interval, 1.239-3.219; P = 0.0045) and tumor grade (hazard ratio, 2.117; 95% confidence interval, 1.339-3.348; P = 0.0013) assessed by a multivariate analysis stratified by American Joint Committee on Cancer stage and p53 overexpression. Endogeneity testing suggested that nuclear overexpression of p53 and tumor type may influence patient survival through their interactions with Aurora-A/Aurora-B expression and tumor grade. Copyright ? 2009 American Association for Cancer Research.
Other Subjects
aurora A kinase; aurora B kinase; protein aurora; protein p53; regulator protein; survivin; unclassified drug; adult; aged; article; bile duct carcinoma; biliary tract cancer; cancer staging; cancer survival; controlled study; female; human; major clinical study; male; priority journal; protein blood level
Publisher
American Association for Cancer Research Inc.
Type
journal article