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

Our plain-English summary of Glypican-1 immunohistochemistry is a novel marker to differentiate epithelioid mesothelioma from lung adenocarcinoma, by V.J. Amatya, K. Kushitani, Y. Kai, et al (Modern Pathology, 2018).

The study

• Authors: V.J. Amatya, K. Kushitani, Y. Kai, R. Suzuki, Y. Miyata, M. Okada, Y. Takeshima
• Journal: Modern Pathology
• Published: 2018;31(5):809-815
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

This laboratory study, by pathologists at Hiroshima University in Japan, tested whether staining tissue for a protein called glypican-1 could help tell epithelioid mesothelioma apart from lung adenocarcinoma, two cancers that can look alike under the microscope. The authors stained archived tissue from 82 epithelioid mesotheliomas and 97 lung adenocarcinomas. Sarcomatoid mesothelioma was not included. Glypican-1 was found in all 82 mesotheliomas, and 56 of them stained in more than half of the tumor cells. Only 3 of the 97 lung adenocarcinomas showed it, focally and weakly. This gave glypican-1 a sensitivity of 100%, a specificity of 97% and an accuracy of 98%. For comparison, the established mesothelioma marker calretinin also stained 18 of 97 (19%) lung adenocarcinomas, and D2-40 stained 7 of 97 (7%). WT1 stained no adenocarcinomas but only 65 of 82 (79%) mesotheliomas. The authors concluded that glypican-1 performed better than calretinin, D2-40 and WT1, and they recommended adding it as a positive marker of epithelioid mesothelioma. They noted that sarcomatoid mesothelioma and other cancers still need study. The study did not examine asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (immunohistochemistry) study of the diagnostic performance of a tissue marker, using archived pathology specimens
• Who was studied: Archived tissue from 82 epithelioid mesotheliomas and 97 lung adenocarcinomas, Department of Pathology, Hiroshima University, Japan. No sarcomatoid mesotheliomas were included. Collection dates are not given.
• Exposure: Not an asbestos exposure study. The factor tested was staining for glypican-1 (a commercially available antibody), compared with calretinin, D2-40, WT1, CEA, claudin 4, TTF-1 and napsin-A. No asbestos exposure information is reported.
• Main results:
  • Glypican-1 was present in all 82 (100%) epithelioid mesotheliomas, whatever their growth pattern. Scores were 3+ in 56 cases, 2+ in 24 cases and 1+ in 2 cases.
  • Glypican-1 was absent in 94 of 97 lung adenocarcinomas. Only 3 showed focal, weak staining (score 1+).
  • For telling epithelioid mesothelioma from lung adenocarcinoma, positive glypican-1 staining had 100% sensitivity, 97% specificity and 98% accuracy.
  • Calretinin was present in 81 (99%) mesotheliomas, but also in 18 of 97 (19%) lung adenocarcinomas.
  • D2-40 was present in 79 (96%) mesotheliomas, and also in 7 of 97 (7%) lung adenocarcinomas.
  • As stated in the results text, calretinin and D2-40 had sensitivities of 99% and 96%, but specificities of only 81% and 93%.
  • WT1 had 100% specificity (no lung adenocarcinoma stained), but its sensitivity was 79% (65 of 82 mesotheliomas).
  • The lung adenocarcinoma markers CEA, claudin 4, TTF-1 and napsin-A were absent from all 82 epithelioid mesotheliomas.
• The authors' conclusion: The authors concluded that glypican-1 is a new positive marker of epithelioid mesothelioma, with better sensitivity and specificity than calretinin, D2-40 and WT1 for telling it apart from lung adenocarcinoma. They recommended including it for this differential diagnosis.
• Limitations the authors state:
  • The study did not include sarcomatoid mesothelioma or other human carcinomas and sarcomas.
  • The reason mesothelial cells express glypican-1 is not known, and further biological and functional analysis is needed.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Immunohistochemistry, Epithelioid, Mesothelioma, Lung Adenocarcinoma, Malignant Mesothelioma, Calretinin, Podoplanin (D2-40).

Related studies

• Glypican-1 immunohistochemistry does not separate mesothelioma from pulmonary adenocarcinoma — K. Chiu, L. Lee, et al. (2018)
• Identification of DAB2 and Intelectin-1 as Novel Positive Immunohistochemical Markers of Epithelioid Mesothelioma by Transcriptome Microarray Analysis for Its Differentiation From Pulmonary Adenocarcinoma — M. Kuraoka, V.J. Amatya, et al. (2017)
• Expression of thrombomodulin, calretinin, cytokeratin 5/6, D2-40 and WT-1 in a series of primary carcinomas of the lung: an immunohistochemical study in comparison with epithelioid pleural mesothelioma — C.E. Comin, L. Novelli, et al. (2014)
• MUC4, a novel immunohistochemical marker identified by gene expression profiling, differentiates pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma — V.J. Amatya, K. Kushitani, et al. (2017)
• Utility and pitfalls of immunohistochemistry in the differential diagnosis between epithelioid mesothelioma and poorly differentiated lung squamous cell carcinoma — K. Kushitani, V.J. Amatya, et al. (2017)
• The diagnostic utility of D2-40, calretinin, CK5/6, desmin and MOC-31 in the differentiation of mesothelioma from adenocarcinoma in pleural effusion cytology — T.S. Hyun, M. Barnes, et al. (2012)

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