Expression of a novel transmembrane carbonic anhydrase isozyme XII in normal human gut and colorectal tumors

Carbonic anhydrase isozyme XII is a recently discovered member of the alpha -carbonic anhydrase gene family with a suggested role in von Hippel-Lindau gene-mediated carcinogenesis. Increased expression of its mRNA has been obs erved in renal and lung carcinomas. This paper presents the localization of CA XII in the normal human gut and in colorectal tumors. Immunohistochemis try performed using a polyclonal antibody raised against truncated CA XII r evealed prominent polarized staining for CA XII in the basolateral plasma m embrane of the enterocytes of the normal large intestine, the reaction bein g most intense in the surface epithelial cuff region. Most colorectal tumor s displayed abnormal expression of CA XII; the most dramatic change was obs erved in the deep parts of the adenomatous mucosa, where the positive immun oreaction clearly increased along with the grade of dysplasia. Adenomas wit h severe dysplasia and carcinomas showed an equal, diffuse staining pattern . The results indicate region-specific regulation of CA XII expression alon g the cranial-caudal axis of the human gut, whereas its diffuse expression in the most malignant tumors seems to correlate with their biological behav ior.