Utility of EMA, XIAP, and GLUT-1 for the Diagnosis of Malignant Mesothelioma in Body Cavity Fluids
J Shen, GS Pinkus, V Deshpande, ES Cibas. Massachusetts General Hospital and Harvard Medical School, Boston; Brigham and Women's Hospital and Harvard Medical School, Boston
Background: The distinction between reactive mesothelial cells and malignant mesothelioma (MM) can be challenging in body cavity fluids. A number of immunohistochemical markers have been proposed to assist with this distinction. Epithelial membrane antigen (EMA) is a promising marker of malignancy but published data reveal conflicting results. Recently, X-linked inhibitor of apoptosis protein (XIAP) and an isoform of glucose transporter (GLUT-1) have been proposed as helpful markers on tissue specimens. This study investigates the effectiveness of EMA and the newer markers XIAP and GLUT-1 to distinguish between reactive and malignant mesothelial cells in cytologic samples.
Design: 73 cases were examined, including 35 cases of MM and 38 cases of benign effusions. The diagnosis was confirmed by histology in all cases of MM. The benign effusions were caused by a variety of non-malignant etiologies in patients with no history of malignancy. Immunohistochemical studies were performed on cell block material from body cavity fluids following heat-induced epitope retrieval (except EMA) using antibodies to EMA (clone E29), XIAP (clone 48/hILP/XIAP), GLUT-1 (clone SPM498, GLUT-1m; rabbit polyclonal, GLUT-1p) and an Envision+ (Dako) detection system. The results were graded using five categories based on the percentage of cells staining: negative (0%), 1+ (<25%), 2+ (25-49%), 3+ (50-74%), and 4+ (75-100%) staining.
Results: At the level of 2+ or higher (25% cells stained), EMA, XIAP, GLUT-1m and GLUT-1p have a sensitivity of 74%, 66%, 40%, 67%, and a specificity of 97%, 58%, 95%, 74%, respectively. At a higher threshold (3+ or higher, i.e., 50% cells stained), they demonstrate a sensitivity of 71%, 46%, 34%, and 51%, and a specificity of 100%, 79%, 95%, and 92%, respectively. Compared to XIAP and GLUT-1, EMA demonstrated better sensitivity and specificity in distinguishing malignant from benign mesothelium, with an area under receiver operating curve (ROC) (AUC) of 0.91, significantly higher than seen for XIAP and GLUT-1m (p<0.05) (Table).
Conclusions: Compared to XIAP and GLUT-1, EMA is a better marker of malignancy for mesothelioma in body cavity fluids, with high specificity and moderate sensitivity.
Table: Comparison of ROCs among different markers
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 66, Wednesday Afternoon