Abstract
BackgroundPancreatic 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.MethodsWe 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.ResultsIn 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).ConclusionThe 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.
Highlights
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
Relationship with clinical outcome In pancreatic cancer calpain-2 was significantly associated with overall survival (P = 0.036) (Figure 2, panel A), which remained significant in multivariate Cox-regression analysis (Hazard Ratio (HR) = 0.342; 95% Confidence Interval = 0.157-0.741; P = 0.007) (Table 3 panel A)
In cancers of the bile duct and ampulla, low cytoplasmic expression of calpastatin was significantly associated with poor overall survival (P = 0.012) (Figure 3, panel C), which remained significant in multivariate Cox-regression analysis (HR = 0.595; 95% Confidence Interval (95% CI) = 0.365-0.968; P = 0.037) (Table 3 panel B)
Summary
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. The expression of a number of proteins has been shown to be associated with poor survival of mechanisms which can promote calpain activity by reducing the concentration of calcium ions required for activation; these include autolysis of the catalytic subunit, interaction with phospholipids, and phosphorylation [9,10,11]. The aims of the current study were to investigate the expression levels of calpastatin, and of the catalytic subunits of μ-calpain and m-calpain in tumours from pancreatic, bile duct and ampullary cancer patients. We aimed to determine the importance of expression in terms of associations with clinicopathological variables and clinical outcome
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