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


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).


CONCLUSIONS
BubR1 expression is a novel, independent adverse prognostic factor after pancreatoduodenectomy of pancreatobiliary-type adenocarcinomas.
Gladhaug
Ivar P
IP
Faculty of Medicine, University of Oslo, and Rikshospitalet University Hospital, Oslo, Norway. ivar.gladhaug@rikshospitalet.no
Westgaard
Arne
A
Schjølberg
Aasa R
AR
Burum-Auensen
Espen
E
Pomianowska
Ewa
E
Clausen
Ole Petter F
OP
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D064127:Aurora Kinases; D014408:Biomarkers, Tumor / Q000032:analysis*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D064246:Mad2 Proteins; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016577:Pancreaticoduodenectomy; D011379:Prognosis; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D012097:Repressor Proteins / Q000096:biosynthesis; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D012097:Repressor Proteins; D064127:Aurora Kinases; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases