Combined use of novel epithelial (MOC-31) and mesothelial (HBME-1) immunohistochemical markers for optimal ®rst line diagnostic distinction between mesothelioma and metastatic carcinoma in pleura C Gonza Âlez-Lois, C Ballestõ Ân, M T Sotelo, F Lo Âpez-Rõ Âos, M D Garcõ Âa-Prats & V Villena Department of Pathology, Doce de Octubre University Hospital, Madrid, Spain Date of submission 23 June 2000 Accepted for publication 12 November 2000 Gonza Âlez-Lois C, Ballestõ Ân C, Sotelo M T, Lo Âpez-Rõ Âos F, Garcõ Âa-Prats M D & Villena V (2001) Histopathology 38, 528±534 Combined use of novel epithelial (MOC-31) and mesothelial (HBME-1) immunohistochemical markers for optimal ®rst line diagnostic distinction between mesothelioma and metastatic carcinoma in pleura Aims: To determine the value of immunohistochemistry in differentiation of malignant pleural mesothelioma from carcinoma in a pleural biopsy we optimized a double panel of MOC-31 and HBME-1 and compared the results with others from the literature. Methods and results: A multi-antibody panel was applied to biopsy samples from 44 cases of malignant pleural mesothelioma and 23 cases of carcinoma metastatic to the pleura. We used monoclonal antibodies against keratins, epithelial membrane antigen (EMA), epithelial antigen Ber-EP4, carcinoembryonic antigen (CEA), tumour-associated glycoprotein (B72.3), LeuM1, vimentin, desmin, epithelial related antigen (MOC-31) and mesothelial cell (HBME-1). Positivity for MOC-31 and Ber-EP4 was found to have the highest nosologic sensitivity (94.1% and 84.6%, respectively) and speci- ®city (86.3% both antibodies) for carcinoma. Positive staining for HBME-1 and vimentin had the highest sensitivity (90.9% and 100%, respectively) and speci- ®city (91.3% and 60%, respectively) for mesothelioma. A two-marker antibody panel with HBME-1 and MOC- 31 was the most ef®cient for the distinction between carcinoma and malignant pleural mesothelioma. Conclusion: A combination of MOC-31 (an anti- epithelial marker) and HBME-1 (an anti-mesothelial marker) has a diagnostic ef®ciency of 76.1% for the distinction between carcinoma and mesothelioma in pleura. Keywords: carcinoma, immunohistochemistry, malignant mesothelioma Introduction Because the microscopic features of malignant pleural mesothelioma and metastatic carcinoma in the pleura are overlapping, the use of ancillary techniques is mandatory in this setting to render the correct diagnosis. Immunohistochemistry is the most frequently used procedure because it can be carried out on formalin- ®xed and paraf®n-embedded tissue samples, maintain- ing enough sensitivity and speci®city. 1±3 A previous study from our group tested a panel of monoclonal antibodies (against keratins, epithelial membrane anti- gen, epithelial antigen Ber-EP4, carcinoembryonic antigen, tumour-associated glycoprotein, LeuM1, CD30, vimentin and desmin) for the distinction between malignant mesothelioma and carcinoma in pleural biopsies. A combination of Ber-EP4 and vimentin provided the most speci®c and sensitive pairs of markers to make this diagnosis. 2 Based on this approach, we have evaluated another group of pleural tumours (44 malig- nant mesotheliomas and 23 metastatic carcinomas) with a similar panel of antibodies, including two recently available anti-mesothelioma (HBME-1) and anti-carcin- oma (MOC-31) monoclonal antibodies. In addition, the literature on these novel antibodies is reviewed. Address for correspondence: Dr M T Sotelo, Departamento de Anatomõ Âa Patolo Âgica, Hospital Universitario 12 de Octubre, Carretera de Andalucõ Âa km 5,4, 28041 Madrid, Spain. Ó 2001 Blackwell Science Limited. Histopathology 2001, 38, 528±534