The significance of carbonic anhydrase expression in human colorectal cancer

Background: Carbonic anhydrase isoenzymes I and II are present in normal colorectal mucosa. This study aimed to determine if carbonic anhydrase is present in colorectal cancer and what is its potential clinical significance. Methods: The messenger RNA (mRNA) and protein expression of carbonic anhydrase isoenzyme I were analyzed in fresh specimens of colorectal adenocarcinoma by Northern and Western blots, respectively. The immunohistochemical expression was subsequently studied in a larger number of formalin-fixed surgical specimens. Results: All of 30 normal colon samples had a strong RNA hybridization signal. Only 4 of 39 paired colorectal cancer and none of 9 normal liver samples had detectable levels of carbonic anhydrase mRNA. Isoenzyme I protein expression showed similar results. In a separate group of patients, immunohistochemical studies showed that 16 of 96 colorectal tumors had positive staining cells. All positive tumors were well or moderately differentiated carcinomas (P < 0.05). When analyzed retrospectively, immunoreactive cases were more likely to be in a group with a good outcome (P < 0.01) and to lack vascular invasion (P < 0.01) than negative cases. Conclusions: The majority of colorectal cancers do not express carbonic anhydrase isoenzyme I. The presence of any isoenzyme I-positive immunoreactive cancer cells may be associated with a more favorable outcome in colorectal cancer.