American Association for Cancer Research, Cancer Epidemiology, Biomarkers & Prevention, 2(18), p. 417-423, 2009
DOI: 10.1158/1055-9965.epi-08-0691
Full text: Download
Mitosis dysregulation is common in cancers. This study explored the nuclear expression patterns and prognostic significance of mitotic regulatory proteins, including Aurora kinases, survivin, and p53, in biliary tract cancer ( BTC). Archival tumor samples from 161 BTC patients who underwent surgery were 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 p 53 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. ; 流行病學研究所 ; 公共衛生學院 ; 流行病學與預防醫學研究所 ; 公共衛生學院 ; 附設醫院醫學研究部 ; 醫學院附設醫院 ; 期刊論文