Expression of the calpain system is associated with poor clinical outcome in gastro-oesophageal adenocarcinomas.

Background: Surgery is critical in the management of gastro-oesophageal cancer, and the addition of neo-adjuvant chemotherapy has proved to be of benefit. The calpain system has been implicated in tumour progression and response to various anti-cancer therapies, and therefore expression of the system was determined in this tumour type.

Methods: Two cohorts of gastro-oesophageal adenocarcinomas were investigated for calpain-1, calpain-2, calpain-9 and calpastatin expression using conventional immunohistochemistry. 88 patients who received neo-adjuvant chemotherapy and 140 patients who received surgery alone were investigated using a tissue microarray approach.

Results: Calpain-1, calpain-2 and calpastatin expression was associated with adverse cancer-specific survival in the neo-adjuvant cohort (P = 0.004, P = 0.001 and P = 0.012 respectively); which remained significant in multivariate analysis (Hazard ratio (HR) = 0.337; 95% confidence interval (CI) = 0.140-0.81; P = 0.015, HR = 0.375; 95% CI = 0.165-0.858; P = 0.020 and HR = 0.481; 95% CI = 0.257-0.900; P = 0.022 respectively). Calpain-1 and calpastatin expression was also associated with adverse cancer specific survival in the primary surgery cohort (P = 0.001 and P = 0.013 respectively); which remained significant in multivariate analysis (HR = 0.309; 95% CI = 0.159-0.601; P = 0.001 and HR = 0.418; 95% CI = 0.205-0.850; P = 0.016 respectively). Calpain-9 expression was not associated with cancer-specific survival in the neo-adjuvant and primary surgery cohorts.

Conclusion: Determining the expression levels of calpain-1, calpain-2 and calpastatin may provide clinically relevant prognostic information for gastro-oesophageal adenocarcinomas; these findings warrant further studies in larger cohorts of patients.