Expression of the membrane-associated carbonic anhydrase isozyme XII in the human kidney and renal tumors

Carbonic anhydrase isozyme XII (CA XII) is a novel membrane-associated prot ein with a potential role in von Hippel-Lindau carcinogenesis. Although Nor thern blotting has revealed positive signal for CA XII in normal human kidn ey, this is the first study to demonstrate its cellular and subcellular loc alization along the human nephron and collecting duct. Immunohistochemistry with a polyclonal antibody (PAb) raised against truncated CA XII revealed distinct staining in the basolateral plasma membrane of the epithelial cell s in the thick ascending limb of Henle and distal convoluted tubules, and i n the principal cells of the collecting ducts. A weak basolateral signal wa s also detected in the epithelium of the proximal convoluted tubules. In ad dition to the normal kidney specimens, this immunohistochemical study inclu ded 31 renal tumors. CA XII showed moderate or strong-plasma membrane-assoc iated expression in most oncocytomas and clear-cell carcinomas. The segment al, cellular, and subcellular distribution of CA XII along the human nephro n and collecting duct suggests that it may be one of the key enzymes involv ed in normal renal physiology, particularly in the regulation of water home ostasis. High expression of CA XII in some renal carcinomas may contribute to its role in von Hippel-Lindau carcinogenesis.