HBME-1, MOC-31, WT1 and calretinin: an assessment of recently described markers for mesothelioma and adenocarcinoma

Our plain-English summary of HBME-1, MOC-31, WT1 and calretinin: an assessment of recently described markers for mesothelioma and adenocarcinoma, by J. Oates, C. Edwards (Histopathology, 2000).

The study

• Authors: J. Oates, C. Edwards
• Journal: Histopathology
• Published: 2000;36(4):341-7
• Cited by: 106 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aims: To evaluate HBME-1, WT1, calretinin and MOC-31 in the differential diagnosis of pleural mesothelioma and adenocarcinoma of the lung.

Methods And Results: Paraffin-embedded formalin-fixed blocks from six reactive pleuras, 42 mesotheliomas and 40 adenocarcinomas were used. Sections were stained for Leu-M1, HBME-1, calretinin, WT1 and MOC-31. Leu-M1 was positive or equivocal in 34% of mesotheliomas and in 78% of adenocarcinomas; reactive pleuras were all negative. HBME-1 was positive or equivocal in 76% of mesotheliomas and in 73% of adenocarcinomas; five reactive pleuras were positive. Calretinin was positive or equivocal in 92% of mesotheliomas and in 73% of adenocarcinomas; two reactive pleura were equivocal and four were positive. WT1 was positive or equivocal in 72% of mesotheliomas (excluding autopsy cases) and in 20% of adenocarcinomas; all reactive pleuras were positive. MOC-31 was positive or equivocal in 5% of mesotheliomas and in 90% of adenocarcinomas; all reactive pleuras were negative. The reaction with Leu-M1 was graded as equivocal in 25% of the adenocarcinomas. All 24 of the autopsy cases of mesothelioma were negative for WT1 and in many operative specimens only the periphery was stained.

Conclusions: Neither calretinin nor HBME-1 are sufficiently discriminatory to be of use, even as members of a panel of antibodies. WT1 shows some promise, but it cannot be used on autopsy material. The utility of MOC-31 is confirmed, and outperforms Leu-M1.

In plain English

This UK laboratory study tested whether four antibody stains (HBME-1, WT1, calretinin and MOC-31) help tell pleural mesothelioma apart from lung adenocarcinoma involving the pleura. It compared them with an established stain, Leu-M1. The authors stained archived tissue from 42 mesotheliomas (17 taken at autopsy), 40 lung adenocarcinomas and six samples of non-cancerous (reactive) pleura. The study did not examine asbestos exposure. MOC-31 was clearly positive in one mesothelioma (2.4%) and in 34 adenocarcinomas (85%). Calretinin and HBME-1 reacted in many tumours of both types: calretinin was positive or equivocal in 70% of adenocarcinomas, and HBME-1 in 73%. WT1 was clearly positive in 38% of mesotheliomas overall but in none of the 17 autopsy cases; with those excluded, 64% were positive. The authors concluded that calretinin and HBME-1 could not be relied on, and that WT1 might be useful in a panel only with careful control of tissue fixation and not on autopsy material. They also concluded that MOC-31 appeared to outperform Leu-M1.

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 (immunohistochemistry) on archived tissue, comparing four newer antibody stains with the established stain Leu-M1; slides were read independently by two observers
• Who was studied: Archived specimens from the Department of Histopathology, Birmingham Heartlands Hospital, UK: 42 mesotheliomas (17 autopsy specimens, the rest large open biopsies or resections; 26 epithelioid, 8 sarcomatoid, 6 mixed, 2 desmoplastic), 40 pulmonary adenocarcinomas, and 6 reactive pleuras from patients treated for persistent pneumothorax. The years of the cases are not stated.
• Exposure: No asbestos exposure was studied. Tissue sections were stained with five antibodies: Leu-M1, HBME-1, MOC-31, WT1 and calretinin.
• Main results:
  • MOC-31 was unequivocally positive in 1 of 42 mesotheliomas (2.4%) and in 34 of 40 adenocarcinomas (85%). It did not react with the reactive pleuras.
  • Leu-M1 was unequivocally positive in 19% of mesotheliomas and equivocal in a further 16%. None of the reactive pleuras were positive.
  • HBME-1 was negative or equivocal in 52% of mesotheliomas and positive or equivocal in 73% of adenocarcinomas. Five of the six reactive pleuras reacted. The authors could not detect a specific staining pattern in any group.
  • Calretinin was negative or equivocal in 33% of mesotheliomas and positive or equivocal in 70% of adenocarcinomas.
  • WT1 was unequivocally positive in 38% of mesotheliomas overall. None of the 17 autopsy cases reacted, and excluding them the proportion positive was 64%.
  • Among the adenocarcinomas, 20% gave a positive or equivocal nuclear reaction for WT1.
  • In larger specimens, WT1 nuclear staining was positive mainly at the edges of the sections, where fixative had penetrated first.
  • In the authors' assessment, MOC-31 appeared to outperform Leu-M1 in distinguishing pleural malignancies.
• The authors' conclusion: The authors concluded that WT1 may be useful as part of a panel of antibodies, but only with careful control of fixation and not on autopsy material. They concluded that neither calretinin nor HBME-1 gave sufficiently consistent or clear-cut results to be relied upon.
• Limitations the authors state:
  • WT1 was detected using microwave antigen retrieval alone, so the authors said negative WT1 results must be interpreted with caution.
  • The authors had no data on how post-mortem autolysis affects WT1 staining in adenocarcinomas.
  • The role of MOC-31 in other types of tumour was not investigated.
  • No scoring system was used; reactions were classed only as positive, negative or equivocal. The authors suggested this may explain why their calretinin results differ from an earlier study.

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: HBME-1, MOC-31, Calretinin, Mesothelioma, Adenocarcinoma, Differential Diagnosis, Pleural Mesothelioma, Pleura.

Related studies

• Calretinin and other mesothelioma markers in synovial sarcoma: analysis of antigenic similarities and differences with malignant mesothelioma — M. Miettinen, J. Limon, et al. (2001)
• Calretinin, thrombomodulin, CEA, and CD15: a useful combination of immunohistochemical markers for differentiating pleural epithelial mesothelioma from peripheral pulmonary adenocarcinoma — C.E. Comin, L. Novelli, et al. (2001)
• Utility of a CEA, CD15, calretinin, and CK5/6 panel for distinguishing between mesotheliomas and pulmonary adenocarcinomas in clinical practice — T. Mohammad, J. Garratt, et al. (2012)
• Combined use of novel epithelial (MOC-31) and mesothelial (HBME-1) immunohistochemical markers for optimal first line diagnostic distinction between mesothelioma and metastatic carcinoma in pleura — C. González-Lois, C. Ballestín, et al. (2001)
• E-cadherin and calretinin: a useful combination of immunochemical markers for differentiation between mesothelioma and metastatic adenocarcinoma — M.P. Leers, M.M. Aarts, et al. (1998)
• Immunohistochemical panels for differentiating epithelial malignant mesothelioma from lung adenocarcinoma: a study with logistic regression analysis — R. Carella, G. Deleonardi, et al. (2001)

Browse more research in Histopathology, or return to medical research.