The specificity of HEG1 as mesothelioma marker depends on the differential diagnosis

The objective of this study was to analyze the diagnostic role of HEG homolog 1 (HEG1) in cancers affecting the serosal cavities. HEG1 protein expression by immunohistochemistry was analyzed in 534 specimens (341 effusions and 193 surgical specimens). Effusions consisted of 151 tubo-ovarian carcinomas, 59 breast carcinomas, 44 mesotheliomas, 37 lung carcinomas, 29 uterine corpus and cervical carcinomas, 17 gastrointestinal carcinomas and 4 genitourinary carcinomas. Surgical specimens consisted of 139 tubo-ovarian carcinomas, 42 mesotheliomas, 7 multicystic mesothelial proliferations and 5 papillary mesothelial tumors. HEG1 expression was found in 43/44 (98%) mesothelioma effusions and 39/42 (93%) surgical mesothelioma specimens, as well as all multicystic and papillary mesothelial tumors. HEG1 was infrequently expressed in breast carcinoma (4/59; 7%), lung carcinoma (2/37; 5%) and cervical/uterine carcinoma effusions (3/29; 10%), but was often detected in tubo-ovarian carcinoma effusions (80/151; 53%) and surgical specimens (99/139, 71%). HEG1 was additionally consistently expressed by reactive mesothelial cells in effusions and in endothelial cells in surgical specimens. HEG1 had sensitivity of 95% for diagnosing malignant mesothelioma in all studied specimens, with a specificity of 38% in the differential diagnosis from tubo-ovarian carcinoma and 93% in the differential diagnosis from non-tubo-ovarian carcinomas. Of 179 HEG1-positive carcinomas, 172 expressed the epithelial marker claudin-4. In conclusion, HEG1 is a highly sensitive marker of both benign and malignant mesothelial cells. It shows high specificity in the differentiation of mesothelioma from lung or breast carcinoma but is of little value in differentiating mesothelioma from tubo-ovarian carcinoma. The potential role of HEG1 as vascular marker merits further research.