Abstract
Malignant mesothelioma is a cancer with a poor survival rate. It is difficult to diagnose mesotheliomas because they show a variety of histological patterns similar to those of various other cancers. However, since currently used positive markers for mesotheliomas may show false positives or false negatives, a novel mesothelial positive marker is required. In the present study, we screened 25 claudins and found that claudin-15 is expressed in the mesothelial cells. We made new rat anti-human claudin-15 (CLDN15) monoclonal antibodies that selectively recognize CLDN15, and investigated whether CLDN15 is a good positive marker for malignant pleural mesotheliomas (MPMs) using MPM tissue samples by immunohistochemistry and semi-quantification of the expression level using an immunoreactive score (IRS) method. Of 42 MPM samples, 83% were positive for CLDN15. The positive ratio was equal to or greater than other positive markers for MPMs including calretinin (81%), WT-1 (50%), and D2-40 (81%). In 50 lung adenocarcinoma sections, four cases were positive for CLDN15 and the specificity (92%) was comparable with other markers (90–100%). Notably, CLDN15 was rarely detected in 24 non-mesothelial tumors in the tissue microarray (12/327 cases). In conclusion, CLDN15 can be used in the clinical setting as a positive marker for MPM diagnosis.
Highlights
Malignant mesothelioma is a cancer with a poor survival rate
Several reports suggested that the expression level of the CLDN15 transcript is elevated in malignant pleural mesotheliomas (MPMs) tissues[22,23,24,27], to date there has been no report examining the protein expression of CLDN15 in MPMs
We showed that claudin-15 is the most abundantly expressed claudin in mesothelial tissues and demonstrated that CLDN15 protein is detected at a high level in MPM tissues using newly established anti-human CLDN15 mAbs
Summary
Malignant mesothelioma is a cancer with a poor survival rate. In 50 lung adenocarcinoma sections, four cases were positive for CLDN15 and the specificity (92%) was comparable with other markers (90–100%). Calretinin, WT-1 (Wilms’ tumor 1), D2-40 (Podoplanin) and CK (Cytokeratin) 5/6 are clinically used as positive markers for epithelioid-type MPMs and carcinoembryonic antigen (CEA), claudin-4, thyroid transcription factor (TTF)-1, Napsin A, MOC31 and BerEP4 are used as negative markers. Claudins (CLDNs) are major components of tight junctions, which seal the intercellular spaces between adjacent cells, such as epithelial and endothelial cells They are four-transmembrane proteins with typically ~ 22-kDa molecular weight. Only a few reports on the expression profile of CLDNs in mesothelial tissues e xist[20] It is unknown which CLDN proteins are expressed in human malignant mesothelioma tissues. Several lines of evidence indicate that the expression of CLDN15 mRNA is overexpressed in the epithelioid subtype of MPMs21–24, which accounts for approximately 60% of MPM c ases[25]
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