Carbonic anhydrase IX is expressed in mesothelioma and metastatic clear cell renal cell carcinoma of the lung

Abstract

High immunohistochemical expression of carbonic anhydrase IX (CAIX) is found in clear cell renal cell carcinoma (ccRCC), but no studies have assessed CAIX in metastatic ccRCC (mccRCC) of the lung. As 75% of patients with mccRCC show lung involvement, characterization of protein expression in these lesions is warranted. This investigation analyzed CAIX immunohistochemical expression in pulmonary/pleural tumors including mccRCC (n = 22), mesothelioma (n = 19), squamous cell carcinoma (n = 27), small cell carcinoma (n = 9), and adenocarcinoma (n = 49), as well as other mesothelial lesions (n = 4). Membranous immunoreactivity was semiquantitatively evaluated for percent of cells stained and intensity. All cases of mccRCC (1+, 4.5%; 3+, 95.5%) and mesothelioma (2+, 10.5%; 3+, 89.5%) expressed CAIX. Most cases of lung squamous cell carcinoma (0, 11.1%; 1+, 25.9%; 2+, 22.2%; 3+, 40.7%) and small cell carcinoma were reactive (0, 11.1%; 1+, 22.2%; 2+, 33.3%; 3+, 33.3%), while CAIX was detected less frequently in pulmonary adenocarcinoma (0, 61.2%; 1+, 16.3%; 2+, 12.2%; 3+, 10.2%). In addition, CAIX was positive in adenomatoid tumor (3+, 100%) and mesothelial hyperplasia (3+, 100%). We demonstrate that CAIX is sensitive for mccRCC within the lung and a novel immunohistochemical marker for mesothelial proliferations, notably mesothelioma. Variable immunoreactivity is present among primary pulmonary epithelial tumors. Knowledge of expression overlap between these entities may prevent an incorrect interpretation of immunohistochemical results, particularly when limited tissue is available. As new carbonic anhydrase inhibitors are being evaluated, testing additional tumors for CAIX may lead to novel treatment options.