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.