Immunohistochemical characterisation and WNT signalling pathway in malignant mesothelioma

The aim of this study was to evaluate the use of immunohistochemical staining to differentiate between malignant mesothelioma and lung adenocarcinoma using newly available commercial antibodies in order to increase sensitivity and specificity of diagnosis and to simplify the antibody panel required. Forty-one malignant mesotheliomas and 35 lung adenocarcinomas were studied. Commercial antibodies to Calretinin, E-cadherin, N-cadherin, surfactant protein-A (SP-A), thyroid transcription factor-1 (TTF-1), thrombomodulin, and cytokeratin 5/6 were applied by immunohistochemistry using the streptavidin-biotin peroxidase complex (StABCPx) procedure on formalin-fixed, paraffin-embedded tissue. E-cadherin was expressed in all adenocarcinoma and in 22% of the mesotheliomas. TTF-1 expression was detected in 69% of the adenocarcinomas and none of the mesotheliomas. Positive staining with polyclonal anticalretinin was detected in 80% of the mesotheliomas and 6% of the adenocarcinomas. N-cadherin was expressed in 78% of mesotheliomas mesotheliomas and 6% of the adenocarcinomas. N-cadherin was expressed in 78% of mesotheliomas and 26% of the adenocarcinomas. Thrombomodulin was expressed in 6% of the adenocarcinomas and 53% of the mesotheliomas. Cytokeratin 5/6 expression was detected in 6% of the adenocarcinomas and 63% of the mesotheliomas. Of the antibodies used, E-cadherin was 100% sensitive for pulmonary adenocarcinoma and TFF-1 was 100% specific for pulmonary adenocarcinoma. The application of these two antibodies alone will be adequate for the diagnosis of 69% of adenocarcinomas and 78% of mesotheliomas. Where TFF-1 is negative and E-cadherin is positive, a secondary panel of markers, including BerEP4, CEA, LeuM1 (CD15), Calretinin, cytokeratin 5/6, thrombomodulin, and N-cadherin, is required for differentiation between malignant mesothelioma and pulmonary adenocarcinoma. In addition, the expression of cell adhesion molecules including cadherins, catenins and APC was examined in order to determine whether abnormal of components of the Wnt signalling pathway contribute to the variable phenotype of malignant mesothelioma.