Use of CD30 expression in human malignant mesothelioma as a novel therapeutic target.

Abstract

e18526 Background: CD30 antigen is important in the diagnosis of Hodgkin’s disease (HD) and anaplastic large cell lymphoma (ALCL). CD30 is a cytokine receptor that belongs to the tumor necrosis factor superfamily (TNFRSF8) and acts as a positive regulator of apoptosis. The expression of CD30 in malignant mesothelioma is unknown. Given the remarkable success of brentuximab vedotin, an antibody-toxin conjugate directed against CD30 antigen, in treating patients with relapsed HD and ALCL, we undertook a study to validate the incidence of CD30 expression in mesothelioma and to examine its clinical correlates. Furthermore, we performed studies using cultured mesothelioma and non-small cell lung cancer (NSCLC) cell lines to determine the expression and potential targeting of CD30 antigen in vitro. Methods: Patient mesothelioma tissue specimens (n=52) were examined for CD30 expression by immuno-histochemistry (IHC) with an anti-BerH2 antibody (Cell Marque) used for the diagnosis of HD. Staining was assessed by a thoracic pathologist. Mesothelioma (H28, H2052, H2452, 211H) and NSCLC (A549, H1299) cell lines were also grown in culture and examined for CD30 expression by FACS analysis and confocal microscopy using anti-CD30 antibody (Novus Biologicals). Cells were permeabilized with Triton X-100. Results: Positive CD30 expression was noted in six out of 52 total mesothelioma specimens. Five of the six positive tumors demonstrated epithelial histology and were scored as low or intermediate grade. Membrane-associated as well as diffuse cytoplasmic staining was observed. The percentage of tumor cells stained positive varied greatly. Interestingly, no high grade epithelial tumors were scored as CD30 positive. The remaining CD30 positive tumor was a high grade, biphasic metastatic tumor. Confocal analysis of both mesothelioma cultured cells localized CD30 antigen to the cell membrane. Flow cytometry of intact and permeabilized mesothelioma cells supported the idea that CD30 antigen was located on the cell-surface. Conclusions: Our studies validate the presence of CD30 antigen on the cell surface of epithelial-type mesothelioma and indicate that selected mesothelioma patients may derive benefit from brentuximab vedotin (Adcetris).