Down regulation of CAII is associated with tumor differentiation and poor prognosis in patients with pancreatic cancer

Background and Objectives Altered expression of carbonic anhydrase (CA)I and II associated with human carcinogenesis. But there was no definite study investigating their expression for clinical significance in pancreatic cancer and effect of the CA inhibitor acetazolamide (AZ) on regulation biological behavior of pancreatic cancer cells. Methods Immunohistochemistry, immunofluorescence, immunoblot, and qRT-PCR were used to detect CAI, II, and p53 expression. Tumor cell viability, apoptosis, and invasion assays were used to investigate the effect of AZ on pancreatic cancer cells. Results Expression of CAI and p53 was increased in pancreatic cancer than that in paired non-cancerous tissues (P=0.021; P=0.007), whereas CAII was down-regulated in pancreatic cancer (P=0.001). CAI overexpression was associated with tumor differentiation and negatively with vascular invasion (P=0.015 and P=0.018, respectively), while overexpression of CAII was associated with tumor differentiation (P=0.017) and a better prognosis of pancreatic cancer patients (P=0.017), and was an independent prognostic indicator (P=0.011). p53 overexpression was related with lymph node metastasis (P=0.032) and TNM stage (P=0.016). Treatment with AZ inhibited tumor cell validity, invasion, and induced apoptosis in some of six pancreatic cancer cells. Conclusion This study suggests the clinical significance of CAI, CAII and p53 expression in pancreatic cancer and provides evidence for AZ as a potential target for controlling pancreatic cancer. J. Surg. Oncol. 2013;107:536543. (c) 2012 Wiley Periodicals, Inc.