Immunohistochemical Reevaluation of Carbonic Anhydrase IX (CA IX) Expression in Tumors and Normal Tissues

Objectives: To immunohistochemically evaluate the carbonic anhydrase IX (CA IX) expression on 1,551 cases of tumors and normal tissues from various organs. Methods: Immunohistochemical evaluation of the expression of CA IX was performed on 1,125 malignant tumors, 69 benign neoplasms, and 322 normal tissues on tissue microarray sections and 18 intrahepatic cholangiocarcinomas (ICCs) and 17 hepatocellular carcinomas (HCCs) on routine sections. Results: There was overexpression of CA IX in clear cell renal cell carcinoma (CRCC) (88%, 68/77). Twenty-six (90%) of 29 ICCs were positive. In contrast, only 5 (15%) of 34 HCCs were focally positive. No staining was seen in chromophobe renal cell carcinoma (ChRCC), oncocytoma, seminoma, or carcinomas of the breast, thyroid, or prostate. All normal renal tubules except one case showed no staining. Conclusions: These data demonstrate the diagnostic utility of CA IX in (1) differentiating CRCC from ChRCC and oncocytomas, (2) distinguishing low-grade CRCC from normal renal tubules in small samples, (3) separating ICC from HCC, and (4) identifying metastatic CRCC from other metastases with clear cell features.