Nuclear Overexpression of Mitotic Regulatory Proteins in Biliary Tract Cancer: Correlation with Clinicopathologic Features and Patient Survival

Abstract

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 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. (Cancer Epidemiol Biomarkers Prev 2009;18(2):417 -23)

Significance of Aurora B overexpression in hepatocellular carcinoma. Aurora B Overexpression in HCC

“…The multivariate analysis confirmed that Aurora B overexpression was an independent risk factor associated with ETR (OR, 4.679; P = 0.0011; Table 2). These findings are consistent with the correlation of Aurora B overexpression with poor tumor differentiation and worse patient survival in thyroid [32], prostate [33], and hepatobiliary cancers [34,35]. Taken together, our findings suggest that Aurora B overexpression serves as a useful marker predicting ETR and hence poor prognosis.…”

High proliferation index, as determined by immunohistochemical expression of Aurora kinase B and geminin, indicates poor prognosis in neuroblastomas

“…Univariable analysis showed high AURKB and GMNN PI to be associated with a significantly worse prognosis in terms of OS and EFS, in agreement with publicly available NB gene expression array data (R2: microarray analysis and visualization platform (http://r2.amc.nl)). Our data are also in line with studies that showed an association between increased immunohistochemical expression of AURKB and shorter survival in head and neck [31], laryngeal [32], lung [33], hepatocellular [34], biliary tract [35], endometrial [36], and ovarian cancer [37]. Similarly, our results are consistent with association between high GMNN level and shorter survival in breast [38], penile [39], renal cell [40], and other cancers, reviewed by Kapoor [41] and Petropoulou et al [20].…”

Proliferation Potential-Related Protein Promotes the Esophageal Cancer Cell Proliferation, Migration and Suppresses Apoptosis by Mediating the Expression of p53 and Interleukin-17

“…Some studies demonstrated that serum antip53 antibodies could be used as early markers for malignant tumors or markers for poor prognosis [21]. Activated p53 can elicit several different cellular responses, including growth arrest, senescence, and apoptosis [22].…”