P2.06-20 Characterization of Claudin15 as a New Diagnostic Marker for Malignant Pleural Mesotheliomas

Abstract

Malignant pleural mesotheliomas (MPMs) is a fatal disease mainly caused by past exposure to asbestos. MPMs are classified into three main histological subtypes: epithelioid, sarcomatoid, and biphasic type. There have been known several immunopathological markers for diagnosing MPMs, but there are not enough reliable markers, which often makes it difficult to diagnose MPMs correctly. In the present study, we investigated whether Claudin15 serves as a diagnostic and therapeutic target for MPMs. Claudins are four-transmembrane proteins and form a protein family consisting 27 members in humans. Specific combination of claudins are differentially expressed in different organs and form tight junctions with different permeability. Expression of Claudin15 has been known to be increased at mRNA level in MPMs. Since 2003 to 2018, 34 patients were diagnosed with MPMs in our hospital. We made a new anti-Claudin15 rat monoclonal antibody, and established a hybridoma clone suitable for IHC. We immunostained 34 tissues with newly established anti-Claudin15 antibody, and compared the staining intensity and occupation with those of Calretinin, a known marker for MPMs. We also immunostained poorly differentiated lung adenocarcinomas, which are sometimes hardly distinguishable with MPMs, with anti-Claudin15 antibody to examine whether Claudin15 staining can distinguish MPMs from adenocarcinomas. Of the 34 cases, the epithelial type was 27 cases, the sarcomatoid type was 1 case, and the biphasic type was 6 cases. The overall expression rate was 53% for Claudin15 and 59% for Calretinin. In terms of histology type, Claudin15 was 50% and Calretinin was 65% in the epithelial type, while Claudin15 was 80% and Calretinin was 40% in the biphasic type. There was only one sarcomatoid type, neither was expressed. Poorly differentiated adenocarcinomas showed no or very low-level expression of Claudin15. Our results suggest that Claudin15 could be a novel diagnostic marker for MPMs, especially for biphasic type. Greater number of cases and further analyses would be required to establish Claudin15 as a diagnostic impact for MPMs in clinical use.