Identification of the MN/CA9 protein as a reliable diagnostic biomarker of clear cell carcinoma of the kidney.

The MN/CA9 protein is a tumor-associated antigen that has been shown to have diagnostic utility in identifying cervical dysplasia and carcinoma. MN/CA9 expression is limited to very few normal tissues. We have now extended those observations to further investigate expression of the MN/CA9 protein in histological sections and fine-needle aspiration biopsy smears of normal kidney, benign renal cell lesions, all categories of renal cell carcinomas (clear/granular/spindle cell, chromophilic cell, chromophobic cell, and collecting duct cell RCCs), metastatic RCCs, and non-renal cell clear cell adenocarcinomas. We have found that high levels of MN/CA9 expression is seen in all primary RCCs, cystic RCCs, and metastatic RCCs, with the exception of two cases of the chromophobe cell type, which were MN/CA9 negative. Identical MN/CA9 immunostaining was also observed in the aspiration cytological smears. In contrast, all benign lesions, including pyelonephritis, renal cysts, adenomas, oncocytomas, and normal kidney, did not express the MN/CA9 protein. Thus, we conclude that MN/CA9 protein expression could serve as a valuable adjunct to the cytological and histological diagnosis of benign renal cysts versus cystic RCC, adenoma versus RCC, and oncocytoma versus granular cell RCC. Diffuse membraneous staining of all RCCs (with the exception of chromophobic cell RCC) suggests that MN/CA9 protein expression might have an important clinical utility in the early detection and treatment of RCC. Absence of MN/CA9 expression in non-renal cell clear cell adenocarcinoma also indicates that MN/CA9 protein expression may be used as a differential diagnostic biomarker of metastatic clear cell RCC.