Membranous HEG1 expression is a useful marker in the differential diagnosis of epithelioid and biphasic malignant mesothelioma versus carcinomas

Our plain-English summary of Membranous HEG1 expression is a useful marker in the differential diagnosis of epithelioid and biphasic malignant mesothelioma versus carcinomas, by K. Hiroshima, D. Wu, E. Koh, et al (Pathology International, 2021).

The study

• Authors: K. Hiroshima, D. Wu, E. Koh, Y. Sekine, D. Ozaki, T. Yusa, T. Nakazawa, S. Tsuji, Y. Miyagi, A.E. Walts, A.M. Marchevsky, A.N. Husain, K. Imai
• Journal: Pathology International
• Published: 2021;71(9):604-613
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Sialylated HEG1 has been reported as a highly specific and sensitive mesothelioma marker but a comprehensive evaluation of its expression in carcinomas in different organs, various sarcomas and reactive mesothelial proliferations has not been reported. The aim of this study was to evaluate the clinical applicability of HEG1 as a marker in the diagnosis of mesothelioma. HEG1 immunoreactivity was evaluated in whole sections of 122 mesotheliomas, 75 pulmonary carcinomas, 55 other carcinomas, 16 mesenchymal tumors, and 24 reactive mesothelial proliferations and in tissue microarrays containing 70 epithelioid (EM), 36 biphasic (BM), and 2 sarcomatoid mesotheliomas (SM). In whole sections and tissue microarrays, respectively, membranous HEG1 was expressed in 93.0% and 85.5% of EM, 81.3% and 69.4% of BM, 0% and 0% of SM. HEG1 was not expressed in pulmonary adenocarcinomas. HEG1 was expressed as cytoplasmic immunoreactivity in pulmonary squamous cell carcinomas (21.7%). Membranous HEG1 staining was seen in ovarian carcinomas (66.7%), thyroid carcinomas (100%), reactive conditions (16.7%), and mesenchymal tumors (18.8%). The sensitivity of membranous HEG1 expression to distinguish EM/BM from all carcinomas was 88.8%. The specificity for the differential diagnosis between EM/BM and all carcinomas and pulmonary carcinomas was 92.3% and 98.7%, respectively.

© 2021 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

In plain English

This laboratory study, by pathologists in Japan and the United States, tested whether a tissue stain for a protein called HEG1 helps tell malignant mesothelioma apart from other cancers. It did not study asbestos exposure. The authors stained archived tissue from 293 cases, including 122 mesotheliomas, 130 carcinomas from the lung and other organs, 16 mesenchymal tumors and 24 reactive mesothelial proliferations. They also stained tissue microarrays (small tissue cores) from other mesotheliomas. In whole sections, HEG1 stained the cell surface (membranous staining) in 53 of 57 (93.0%) epithelioid and 26 of 32 (81.3%) biphasic mesotheliomas. It did so in none of 25 sarcomatoid mesotheliomas. None of 36 lung adenocarcinomas stained. Ten of 130 carcinomas showed membranous staining, including 6 of 9 ovarian serous and all 3 thyroid carcinomas. For separating epithelioid or biphasic mesothelioma from all carcinomas, sensitivity was 88.8% and specificity 92.3%. Specificity was 98.7% against lung carcinomas alone. The authors concluded the stain performs well for this purpose. They added that it cannot separate mesothelioma from ovarian serous or thyroid carcinoma, or from reactive mesothelial proliferation. They noted the cases were retrospective and not consecutive.

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: Retrospective laboratory (immunohistochemistry) study of archived, non-consecutive tissue samples
• Who was studied: Whole tissue sections from 293 analyzed cases: 122 malignant mesotheliomas (57 epithelioid, 32 biphasic, 25 sarcomatoid, 3 desmoplastic, 3 transitional, 1 with heterologous elements, 1 lymphohistiocytoid), 1 well-differentiated papillary mesothelioma, 75 pulmonary carcinomas, 55 nonpulmonary carcinomas, 16 mesenchymal tumors and 24 reactive mesothelial proliferations. These came from archives at Tokyo Women's Medical University Yachiyo Medical Center, Chiba Rosai Hospital and Cedars-Sinai Medical Center. Tissue microarrays of pleural and peritoneal mesotheliomas were provided by one author. No dates of the cases are given.
• Exposure: No asbestos exposure was studied. The study tested immunohistochemical staining with a monoclonal anti-sialylated HEG1 antibody (SKM9-2). It compared this with the conventional mesothelial markers calretinin, WT1 and podoplanin.
• Main results:
  • In whole sections, membranous HEG1 staining was seen in 53 of 57 (93.0%) epithelioid mesotheliomas.
  • In whole sections, membranous HEG1 staining was seen in 26 of 32 (81.3%) biphasic mesotheliomas.
  • 20 of 25 (80.0%) sarcomatoid mesotheliomas showed cytoplasmic staining, and none showed membranous staining.
  • In tissue microarrays, membranous HEG1 staining was seen in 59 of 69 (85.5%) epithelioid and 25 of 36 (69.4%) biphasic mesotheliomas.
  • HEG1 was not expressed in any of 36 pulmonary adenocarcinomas.
  • HEG1 was focally expressed, cytoplasmic only, in 5 of 23 (21.7%) pulmonary squamous cell carcinomas.
  • Membranous staining occurred in 6 of 9 (66.7%) ovarian serous carcinomas and in all 3 thyroid carcinomas.
  • For epithelioid or biphasic mesothelioma versus all carcinomas, 10 of 130 carcinomas were positive. This gave a sensitivity of 88.8% and a specificity of 92.3%.
  • For epithelioid or biphasic mesothelioma versus pulmonary carcinomas only, sensitivity was 88.8% and specificity was 98.7%.
  • 3 of 16 (18.8%) mesenchymal tumors showed membranous HEG1 staining.
  • Among mesotheliomas that stained with only one conventional mesothelial marker, HEG1 was positive in 71.4%.
• The authors' conclusion: The authors concluded that membranous HEG1 staining shows excellent sensitivity and specificity in distinguishing epithelioid or biphasic mesothelioma from carcinomas, especially pulmonary carcinomas. They also concluded that it cannot distinguish epithelioid mesothelioma from ovarian serous carcinoma or thyroid carcinoma, and that it is not useful for distinguishing mesothelioma from reactive mesothelial proliferation.
• Limitations the authors state:
  • The study was retrospective, and the cases were selected from archives and were not consecutive.
  • Tumors from several organs were not represented.
  • The sensitivity and specificity figures cannot be taken as universal or applicable to daily pathology practice.

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: HEG1, Differential Diagnosis, Epithelioid, Biphasic Mesothelioma, Malignant Mesothelioma, Carcinoma, Mesothelioma, Sarcoma.

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• 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 "Brescia panel" (Claudin-4 and BRCA-associated protein 1) in the differential diagnosis of mesotheliomas with epithelioid features versus metastatic carcinomas — L. Bernardi, T. Bizzarro, et al. (2021)
• Loss of BAP1 expression is very rare in peritoneal and gynecologic serous adenocarcinomas and can be useful in the differential diagnosis with abdominal mesothelioma — J. Andrici, J. Jung, et al. (2016)
• NY-ESO-1 expression in synovial sarcoma and other mesenchymal tumors: significance for NY-ESO-1-based targeted therapy and differential diagnosis — J.P. Lai, P.F. Robbins, et al. (2012)

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