Spindle proteins in resected pancreatic head adenocarcinomas: BubR1 is an independent prognostic factor in pancreatobiliary-type tumours.

ABSTRACT

AIMS: Spindle proteins such as Aurora A, Mad2 and BubR1 are important for chromosome segregation during mitosis. Dysfunction of these proteins is implicated in the development of many cancers. The aim was to examine their possible prognostic impact in resected adenocarcinomas in the pancreatic head. METHODS AND RESULTS: Two hundred and eighteen consecutively resected pancreatobiliary-type (n=145) and intestinal-type (n=73) adenocarcinomas involving the pancreatic head were examined for expression of Aurora A, Mad2 and BubR1 by immunohistochemistry on tissue microarrays. Aurora A (P<0.001) and Mad2 (P=0.003) were expressed more often and at higher levels in intestinal-type compared with pancreatobiliary-type tumours, whereas BubR1 was equally expressed in both histological types. Expression of BubR1, Aurora A and Mad2 was not associated with ploidy status. None of the spindle proteins was significantly associated with prognosis in intestinal-type tumours. In pancreatobiliary-type tumours, any BubR1 expression was sufficient to predict poor prognosis (P=0.006), whereas Aurora A and Mad2 expression was not significantly associated with prognosis (P=0.86 and P= 0.87, respectively). On adjusted Cox regression analysis, BubR1 expression independently predicted poor prognosis [P=0.002; hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.26, 2.79)], particularly in small tumours (P=0.001; HR 2.93, 95% CI 1.53, 5.62). CONCLUSION: BubR1 expression is a novel, independent adverse prognostic factor after pancreatoduodenectomy of pancreatobiliary-type adenocarcinomas.