The specificity of HEG1 as mesothelioma marker depends on the differential diagnosis

Our plain-English summary of The specificity of HEG1 as mesothelioma marker depends on the differential diagnosis, by B. Davidson, L.M. Stričak, A. Holth, et al (Virchows Archiv, 2026).

The study

• Authors: B. Davidson, L.M. Stričak, A. Holth, A. Torgunrud, J. Wohlschlaeger, M. Tötsch, A. Bassarova
• Journal: Virchows Archiv
• Published: 2026;488(3):617-626
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The objective of this study was to analyze the diagnostic role of HEG homolog 1 (HEG1) in cancers affecting the serosal cavities. HEG1 protein expression by immunohistochemistry was analyzed in 534 specimens (341 effusions and 193 surgical specimens). Effusions consisted of 151 tubo-ovarian carcinomas, 59 breast carcinomas, 44 mesotheliomas, 37 lung carcinomas, 29 uterine corpus and cervical carcinomas, 17 gastrointestinal carcinomas and 4 genitourinary carcinomas. Surgical specimens consisted of 139 tubo-ovarian carcinomas, 42 mesotheliomas, 7 multicystic mesothelial proliferations and 5 papillary mesothelial tumors. HEG1 expression was found in 43/44 (98%) mesothelioma effusions and 39/42 (93%) surgical mesothelioma specimens, as well as all multicystic and papillary mesothelial tumors. HEG1 was infrequently expressed in breast carcinoma (4/59; 7%), lung carcinoma (2/37; 5%) and cervical/uterine carcinoma effusions (3/29; 10%), but was often detected in tubo-ovarian carcinoma effusions (80/151; 53%) and surgical specimens (99/139, 71%). HEG1 was additionally consistently expressed by reactive mesothelial cells in effusions and in endothelial cells in surgical specimens. HEG1 had sensitivity of 95% for diagnosing malignant mesothelioma in all studied specimens, with a specificity of 38% in the differential diagnosis from tubo-ovarian carcinoma and 93% in the differential diagnosis from non-tubo-ovarian carcinomas. Of 179 HEG1-positive carcinomas, 172 expressed the epithelial marker claudin-4. In conclusion, HEG1 is a highly sensitive marker of both benign and malignant mesothelial cells. It shows high specificity in the differentiation of mesothelioma from lung or breast carcinoma but is of little value in differentiating mesothelioma from tubo-ovarian carcinoma. The potential role of HEG1 as vascular marker merits further research.

© 2026. The Author(s).

In plain English

This laboratory study tested whether staining for a protein called HEG1 helps pathologists tell mesothelioma apart from other cancers that spread to the linings of the chest and abdomen. The authors stained 341 fluid samples (effusions), most from the Norwegian Radium Hospital in Oslo (1998 to 2020) and the rest from Graz and Essen. They also stained surgical specimens, including 139 tubo-ovarian carcinomas and 42 mesotheliomas. HEG1 was found in 43 of 44 mesothelioma effusions and 39 of 42 surgical mesotheliomas. It was also found in 80 of 151 tubo-ovarian carcinoma effusions and 99 of 139 tubo-ovarian surgical specimens, but rarely in breast (4 of 59) or lung (2 of 37) carcinoma effusions. It also stained non-cancerous (reactive) mesothelial cells. Sensitivity for mesothelioma was 95%. Specificity was 38% against tubo-ovarian carcinoma and 93% against other carcinomas. The authors concluded that HEG1 performs well against breast and lung carcinoma but is not useful against tubo-ovarian carcinoma. 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 diagnostic study of immunohistochemical (tissue staining) results on archived effusion and surgical specimens
• Who was studied: 341 malignant effusions (299 from the Norwegian Radium Hospital, Oslo, 1998 to 2020; 22 from Graz, Austria; 20 from Essen, Germany), comprising 151 tubo-ovarian carcinomas, 59 breast carcinomas, 44 mesotheliomas, 37 lung carcinomas, 29 uterine corpus and cervical carcinomas, 17 gastrointestinal carcinomas and 4 genitourinary carcinomas. In addition there were surgical specimens from the Norwegian Radium Hospital: 139 tubo-ovarian carcinomas, 42 mesotheliomas (25 pleural, 17 peritoneal), 7 multicystic mesothelial proliferations and 5 papillary mesothelial tumors.
• Exposure: No asbestos or other exposure was studied. The 'test' examined was staining for the HEG1 protein using the SKM9-2 monoclonal antibody, with claudin-4 staining in HEG1-positive carcinomas.
• Main results:
  • HEG1 was present in 43/44 (98%) mesothelioma effusions and 39/42 (93%) surgical mesothelioma specimens
  • HEG1 was present in 80/151 (53%) tubo-ovarian carcinoma effusions and 99/139 (71%) tubo-ovarian carcinoma surgical specimens
  • HEG1 was infrequent in breast carcinoma effusions (4/59; 7%) and lung carcinoma effusions (2/37; 5%)
  • Across all specimens, HEG1 had 95% sensitivity for diagnosing mesothelioma
  • Specificity was 38% in distinguishing mesothelioma from tubo-ovarian carcinoma
  • Specificity was 93% in distinguishing mesothelioma from non-tubo-ovarian carcinomas
  • Reactive (non-cancerous) mesothelial cells in effusions from patients with metastatic carcinoma consistently stained for HEG1
  • In surgical specimens, endothelial (blood vessel lining) cells consistently stained for HEG1
  • All multicystic mesothelial proliferations and papillary mesothelial tumors were HEG1-positive
  • In effusions, HEG1 staining extent was comparable in pleural and peritoneal mesotheliomas (p = 0.334)
  • Of 179 HEG1-positive carcinomas stained for claudin-4, 172 (96%) expressed claudin-4
  • In tubo-ovarian surgical specimens, HEG1 expression was significantly higher in high-grade and low-grade serous carcinoma than in clear cell carcinoma (p = 0.004)
• The authors' conclusion: The authors concluded that HEG1 is a sensitive mesothelioma marker that performs well in distinguishing mesothelioma from metastatic breast and lung carcinoma, but is not a useful marker for distinguishing mesothelioma from tubo-ovarian carcinoma.
• Limitations the authors state:
  • The comparison of HEG1 expression between tubo-ovarian histotypes in surgical specimens was based on small numbers of low-grade serous and clear cell carcinomas
  • The difference in claudin-4 staining between tubo-ovarian effusions and surgical specimens was not statistically analyzed

Topics

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

Medical terms in this study, explained in our Lexicon: HEG1, Mesothelioma, Differential Diagnosis, Immunohistochemistry, Carcinoma, Reactive Mesothelial Hyperplasia, Claudin-4, Mesothelial Cells.

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