Carbonic anhydrase IX expression in clear cell renal cell carcinomas negatively correlates with the proportion of the granular cell component
Abstract
We read with great interest an article by Leibovich et al addressing the expression of carbonic anhydrase IX (CAIX) in clear cell renal cell carcinomas (ccRCC). CAIX is a catalytically active cell membrane isoform of carbonic anhydrase, which was unexpectedly discovered during the virologic research and may be ectopically expressed by various tumor cells.
The authors evaluated its use as a prognostic marker in ccRCC and presented crucial facts for the interpretation of CAIX immunohistochemistry with the mouse monoclonal antibody M75. Therefore, we cannot fully agree with Leibovich et al that CAIX could be used as a complementary marker for the histopathologic evaluation of small renal mass biopsies.
The authors propose that patients with more than 30% CAIX expression in their renal tumors harbor ccRCC rather than papillary RCC or chromophobe RCC. By analogy with the TMA technique, this could be misleading in small, poorly representative tissue specimens taken from ccRCC with an increased number of granular neoplastic cells.
Because of a high risk of sampling error, the inclusion of CAIX immunohistochemistry in the diagnostic algorithm of renal tumors composed of cells with granular eosinophilic cytoplasm should be avoided. Given that these cells may be present in all common types of RCC (clear cell, papillary, and chromophobe) as well as in renal oncocytomas, the significance of CAIX immunohistochemistry for the differential diagnosis of renal tumors remains limited.