Immunohistochemical analysis of nuclear versus cytoplasmic staining of WT1in malignant mesotheliomas and primary pulmonary adenocarcinomas

Context.-Previous studies have indicated certain immunohistochemical marker s, including WT1, may be helpful in distinguishing adenocarcinomas from mes otheliomas, but to date there are no reliable, widely accepted, commerciall y available antibodies positive in mesotheliomas and negative in adenocarci nomas. We compared the nuclear and cytoplasmic staining patterns of WT1 in these 2 malignancies using a commercially available antibody and examined t he expression of 2 other previously reported positive markers, calretinin a nd thrombomodulin. Methods.-Sixty-seven mesotheliomas and 51 adenocarcinomas, all paraffin emb edded, were retrieved from recent case files. The diagnosis of mesothelioma was based on typical clinical and morphologic features, as well as immunoh istochemistry; electron microscopy had been performed on 16 cases. The diag nosis of adenocarcinoma was based on typical light microscopic findings and a positive stain for mucin. Commercially available antibodies to WT1, thro mbomodulin, and calretinin were applied. Because of the conflict surroundin g calretinin, 2 anticalretinin antibodies (from Chemicon Inc and Zymed Labo ratories) were utilized. Results.-Fifty of 67 mesotheliomas showed strong nuclear staining with WT1. No adenocarcinomas (0/51) showed nuclear staining. Twenty-three of 67 meso theliomas were positive for thrombomodulin, and 35 of 67 mesotheliomas were positive for calretinin with the Chemicon antibody. Nine of 15 mesotheliom as were positive for calretinin with the Zymed antibody. Conclusions.-Thrombomodulin and calretinin did not prove useful in discrimi nating between mesotheliomas and adenocarcinomas. The degree of positivity with calretinin may be dependent on the specific antibody utilized. Nuclear staining for WT1 is highly specific for mesothelioma and, in the appropria te clinical setting, can be a helpful adjunct in the distinction between ad enocarcinomas and mesotheliomas.