title: Calpain system protein expression in carcinomas of the pancreas, bile duct and ampulla.
abstract: BACKGROUND
  Pancreatic cancer, including cancer of the ampulla of Vater and bile duct, is very aggressive and has a poor five year survival rate; improved methods of patient stratification are required.
  
  
  METHODS
  We assessed the expression of calpain-1, calpain-2 and calpastatin in two patient cohorts using immunohistochemistry on tissue microarrays. The first cohort was composed of 68 pancreatic adenocarcinomas and the second cohort was composed of 120 cancers of the bile duct and ampulla.
  
  
  RESULTS
  In bile duct and ampullary carcinomas an association was observed between cytoplasmic calpastatin expression and patient age (P = 0.036), and between nuclear calpastatin expression and increased tumour stage (P = 0.026) and the presence of vascular invasion (P = 0.043). In pancreatic cancer, high calpain-2 expression was significantly associated with improved overall survival (P = 0.036), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.342; 95% confidence interva l = 0.157-0.741; P = 0.007). In cancers of the bile duct and ampulla, low cytoplasmic expression of calpastatin was significantly associated with poor overall survival (P = 0.012), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.595; 95% confidence interval = 0.365-0.968; P = 0.037).
  
  
  CONCLUSIONS
  The results suggest that calpain-2 and calpastatin expression is important in pancreatic cancers, influencing disease progression. The findings of this study warrant a larger follow-up study.
authors.affiliation: Academic Oncology, University of Nottingham, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Storr
authors.forename: Abed M
authors.initials: AM
authors.lastname: Zaitoun
authors.forename: Arvind
authors.initials: A
authors.lastname: Arora
authors.forename: Lindy G
authors.initials: LG
authors.lastname: Durrant
authors.forename: Dileep N
authors.initials: DN
authors.lastname: Lobo
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Madhusudan
authors.forename: Stewart G
authors.initials: SG
authors.lastname: Martin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater / Q000378:metabolism / Q000473:pathology; D001650:Bile Duct Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000096:biosynthesis; D002154:Calpain / Q000032:analysis / Q000096:biosynthesis*; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; C033668:calpastatin; D002154:Calpain