Expression of carbonic anhydrase IX in human pancreatic cancer.

Abstract

Carbonic anhydrase IX has been linked to cancer development and progression. To analyse carbonic anhydrase IX expression and anhydrase inhibition in pancreatic cancer and to correlate these findings with p53 expression and microvessel density. Seventy-seven pancreatic cancers were examined (43 males, 34 females; mean age, 64 years). The anti-carbonic anhydrase IX M75 antibody was used for immunohistochemistry and Western blot analysis. Microvessels were visualized using the anti-CD34 antibody, and p53 expression in cancer cells was assessed with a specific anti-p53 antibody. Quantitative polymerase chain reaction was performed in order to assess carbonic anhydrase IX mRNA levels in the pancreas. Furthermore, pancreatic cancer cell lines were treated with acetazolamide, a carbonic anhydrase inhibitor. In the normal pancreas, carbonic anhydrase IX immunoreactivity was observed at the basolateral membrane of ductal cells in 24 cases (31%). Carbonic anhydrase IX expression was found at the membrane and in the cytoplasm of pancreatic cancer cells in 16 pancreatic cancers (21%). Carbonic anhydrase IX expression was independent of the localization, stage, size, metastases and differentiation of the tumour. p53 expression was significantly more frequent in poorly differentiated cancers (P=0.0323); however, p53 expression and microvessel density were independent of carbonic anhydrase IX expression. Overall, carbonic anhydrase IX expression was not altered in pancreatic cancers vs. adjacent normal pancreatic tissue as assessed by Western blot and quantitative polymerase chain reaction analysis. However, incubation of pancreatic cancer cell lines with acetazolamide led to a significant inhibition of cell proliferation in AsPC-1 and PANC-1 pancreatic cancer cells. Carbonic anhydrase IX expression is observed in both ductal epithelial and cancer cells of the pancreas. Although the expression of carbonic anhydrase IX in pancreatic cancer is not associated with angiogenesis or advanced disease, it may well be a target for carbo-anhydrase inhibitors in a subset of pancreatic cancers.