Glypican-1 immunohistochemistry is a novel marker to differentiate epithelioid mesothelioma from lung adenocarcinoma

Abstract

Histological morphology alone is not sufficient for the pathological diagnosis of malignant mesothelioma. Positive and negative immunohistochemical markers are necessary to differentiate it from lung adenocarcinoma. As calretinin and D2-40, the recognized positive markers of mesothelioma, are expressed in lung adenocarcinoma to some extent, novel markers with high specificity are desirable. In this study, we investigated the applicability of glypican-1 immunohistochemistry to differentiate epithelioid mesothelioma from lung adenocarcinoma. We investigated 82 cases of epithelioid mesothelioma and 97 cases of lung adenocarcinoma for glypican-1 expression by immunohistochemistry using a commercially available antibody. All 82 cases of epithelioid mesothelioma showed glypican-1 expression, most with diffuse and strong reactivity. In contrast, only three cases of lung adenocarcinoma showed focal glypican-1 expression. Glypican-1 expression showed 100 sensitivity, 97% specificity, and a 98% accuracy rate to differentiate epithelioid mesothelioma from lung adenocarcinoma. The sensitivity of glypican -1 immunohistochemistry is as high as that of calretinin and D2-40, and its specificity is far better than that of calretinin and D2-40. Therefore, we recommend including glypican -1 immunohistochemistry as a positive marker of epithelioid mesothelioma.

Glypican-1 immunohistochemistry does not separate mesothelioma from pulmonary adenocarcinoma

“…The H-scores for glypican-1 were comparable between pulmonary adenocarcinomas and mesotheliomas, irrespective of histologic type. Our results differ significantly from those of Amatya et al [9], who reported that glypican-1 was highly sensitive and specific for epithelioid mesotheliomas when differentiating them from pulmonary adenocarcinoma. They reported that all 82 cases of epithelioid mesotheliomas in their study set were positive for glypican-1, while only 3 (3%) of 97 cases of pulmonary adenocarcinoma were positive.…”

“…The diffuse staining observed in essentially all of our cases of pulmonary adenocarcinomas means it is unlikely that focal hotspots of staining are being represented by the cores in the tissue microarrays. Interestingly, cytoplasmic staining in benign mesothelial proliferations was also reported by Amatya et al [9], which was concordant with the findings in our study. In our study, the H-score of benign reactive mesothelial proliferation was significantly lower than that for pulmonary adenocarcinoma, but this is not helpful diagnostically.…”

“…Both studies used the same glypican-1 antibody and antibody dilution. While we used tissue microarrays in comparison to the use of whole tissue sections by Amatya et al [9], tumor heterogeneity is unlikely to explain the discrepancy. The diffuse staining observed in essentially all of our cases of pulmonary adenocarcinomas means it is unlikely that focal hotspots of staining are being represented by the cores in the tissue microarrays.…”

“…IHC was performed on the tissue microarrays with glypican-1 rabbit polyclonal antibody (1:100 dilution; Proteintech Group, Rosemount, IL, USA), the same antibody and dilution used by Amatya et al [9]. Heat-induced epitope retrieval was performed for 30 min with EnVision FLEX TRS high pH buffer (Agilent Technologies, Santa Clara, CA, USA).…”

“…Glypicans are cell-surface-associated proteoglycans that bind signaling factors affecting cell proliferation, mobility, and adhesion, and are upregulated in a variety of tumors [8 and see Discussion]. Recently, Amatya et al reported that IHC with glypican-1 is a highly sensitive marker for epithelioid mesothelioma, and only rarely stains pulmonary adenocarcinoma [9]. Glypican-1 was therefore proposed as a highly sensitive and specific marker for epithelioid mesothelioma when considering pulmonary adenocarcinoma in the differential diagnosis.…”