Caveolin-1 is a novel immunohistochemical marker to differentiate epithelioid mesothelioma from lung adenocarcinoma Vishwa Jeet Amatya, Yukio Takeshima, Hidekazu Kohno, Kei Kushitani, Taketo Yamada, 1 Chikao Morimoto 2 & Kouki Inai Department of Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, 1 Department of Pathology, Keio University, and 2 Division of Clinical Immunology, Advanced Clinical Research Centre, Institute of Medical Sciences, University of Tokyo, Tokyo, Japan Date of submission 2 July 2008 Accepted for publication 16 December 2008 Amatya V J, Takeshima Y, Kohno H, Kushitani K, Yamada T, Morimoto C & Inai K (2009) Histopathology 55, 10–19 Caveolin-1 is a novel immunohistochemical marker to differentiate epithelioid mesothelioma from lung adenocarcinoma Aims: The incidence of mesothelioma is increasing in Europe, Japan and other developing countries. There is difficulty in the accurate diagnosis of mesothelioma and its differentiation from lung adenocarcinoma. Mesothe- lioma shows a complex immunohistochemical profile. Therefore, the use of a immunohistochemical panel that includes both positive and negative mesothelial markers has become a general rule for its accurate diagnosis. However, they are still not sufficient. The aim was to assess the diagnostic utility of caveolin-1 (Cav-1), which is expressed in endothelial cells, alve- olar type I pneumocytes and mesothelial cells, as a novel positive marker of mesothelioma. Methods and results: An immunohistochemical study of 80 cases of epithelioid mesothelioma and 80 cases of lung adenocarcinoma was performed for the analysis of the expression of Cav-1 and other markers. Cav-1 expression with a membranous and ⁄ or cytoplasmic pattern was found in all of the epithelioid mesotheli- oma. Of these, 42 cases (52.5%) showed Cav-1 expression in >50% of tumour cells, 34 cases (42.5%) in 6–50% of tumour cells, and four cases (5.0%) in <5% of tumour cells. In contrast, only six cases (7.5%) of lung adenocarcinoma showed focal Cav-1 expression in the cytoplasm of the tumour cells. The sensitivity and specificity of Cav-1 expression for the differentiation of epithelioid mesothelioma from lung adenocarcinoma were 100 and 92.5%, respec- tively. This is comparable or even superior to that of currently available positive markers such as calretinin or D2-40. Conclusions: Cav-1 is a novel immunohistochemical marker for the differentiation of epithelioid mesotheli- oma from lung adenocarcinoma. Keywords: caveolin-1, differential diagnosis, epithelioid mesothelioma, immunohistochemistry, lung adenocarcinoma Abbreviations: Cav-1, caveolin-1; CEA, carcinoembryonic antigen; SPA, surfactant apoprotein A; TTF, thyroid transcription factor; WT-1, Wilms’ tumour-1 Introduction Mesothelioma is a rare, aggressive, and often deadly malignancy commonly associated with asbestos exposure. 1 Pleural mesothelioma rarely metastasizes until late in its course; however, it can persistently invade adjacent structures such as the chest wall, diaphragm, medias- tinum, and lung parenchyma. The incidence of meso- thelioma has been decreasing in the USA and Canada, but it is still increasing in Europe, Japan and other developing countries. Surgical pathologists, in future, will encounter more diagnostic problems in the dis- tinction between epithelioid mesothelioma and lung Address for correspondence: V J Amatya, Department of Pathology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. e-mail: amatya@hiroshima-u.ac.jp Ó 2009 The Authors. Journal compilation Ó 2009 Blackwell Publishing Limited. Histopathology 2009, 55, 10–19. DOI: 10.1111/j.1365-2559.2009.03322.x