Overexpression of CYP2A6 in human colorectal tumors.

CYP2A6 metabolizes various nitrosamines, such as those in the diet and in tobacco smoke, which have been implicated as risk factors for colorectal tumors. To determine whether changes in expression levels could contribute to their progression, we carried out immunohistochemistry for CYP2A6 in human colon tumors. Colon specimens (n = 53) were diagnosed as adenoma (n = 16), adenocarcinoma (n = 30) or carcinoma in or with adenoma (n = 7). Colon tumor cells showed cytoplasmic granular immunoreactivity for CYP2A6. Adenocarcinomas and adjacent mucosa showed similar highly elevated degrees of CYP2A6 expression, whereas carcinomas in or with adenoma and adenomas showed lesser increases. To further determine whether CYP2A6 mRNA was expressed at the same level as the CYP2A6 protein, we carried out in situ hybridization of CYP2A6 in two cases of adenocarcinoma. In situ hybridization for CYP2A6 revealed mRNA expression in adenocarcinoma cells. The data indicate that CYP2A6 may have important roles in human colorectal tumorigenesis and progression, so that it could be a candidate therapeutic and chemopreventive target for colorectal cancers.