Calretinin, thrombomodulin, CEA, and CD15: a useful combination of immunohistochemical markers for differentiating pleural epithelial mesothelioma from peripheral pulmonary adenocarcinoma

Our plain-English summary of Calretinin, thrombomodulin, CEA, and CD15: a useful combination of immunohistochemical markers for differentiating pleural epithelial mesothelioma from peripheral pulmonary adenocarcinoma, by C.E. Comin, L. Novelli, V. Boddi, et al (Human Pathology, 2001).

The study

• Authors: C.E. Comin, L. Novelli, V. Boddi, M. Paglierani, S. Dini
• Journal: Human Pathology
• Published: 2001;32(5):529-36
• Cited by: 80 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The distinction between pleural epithelial mesothelioma and peripheral lung adenocarcinoma involving the pleura is still an important diagnostic problem for surgical pathologists. The aim of our study was to identify the most specific and sensitive markers for the positive identification of mesothelioma to select a limited, appropriate panel of antibodies to differentiate between mesothelioma and adenocarcinoma. Forty-two cases of epithelial mesotheliomas and 23 cases of pulmonary adenocarcinomas were stained with the following antibodies: anticalretinin, antithrombomodulin, anti-CD44H, and monoclonal antibody HBME-1. We also studied the value of other markers in current use: cytokeratins AE1/AE3 and CAM5.2, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), Ber-EP4, B72.3, and CD15. Of the mesotheliomas, 42 stained for calretinin, 39 (92.8%) for thrombomodulin, 42 stained for CD44H, and 41 (97.6%) stained for HBME-1. Among negative markers, 4 (9.5%) mesothelioma cases stained for CEA, 5 (11.9%) stained for Ber-EP4, 6 (14.2%) stained for B72.3, and 2 (4.7%) stained for CD15. Of the lung adenocarcinomas, 2 (8.7%) cases showed reactivity for calretinin, 5 (21.7%) for thrombomodulin, 13 (56.5%) for CD44H, all for HBME-1, 22 (95.6%) for CEA, 22 (95.6%) for Ber-EP4, 8 (34.7%) for B72.3, and all for CD15. In conclusion, calretinin and thrombomodulin were the most specific positive mesothelial markers, whereas CD44H and HBME-1 showed high sensitivity but very low specificity. Among negative markers, we advocate the use of CEA and CD15 which were the most specific in differentiating mesotheliomas from adenocarcinomas.

In plain English

This laboratory study, from the University of Florence, Italy, tested whether stains that bind to particular proteins (immunohistochemical markers) could tell pleural epithelial mesothelioma apart from lung adenocarcinoma, a lung cancer that can involve the pleura. The authors stained stored surgical tissue from 42 pleural epithelial mesotheliomas and 23 pulmonary adenocarcinomas with a panel of markers. Calretinin stained all 42 mesotheliomas and 2 of 23 adenocarcinomas (sensitivity 100%, specificity 91.3%). Thrombomodulin stained 39 of 42 mesotheliomas and 5 of 23 adenocarcinomas (sensitivity 92.9%, specificity 78.3%). CD44H stained all 42 mesotheliomas and 13 of 23 adenocarcinomas. HBME-1 stained 41 of 42 mesotheliomas and all 23 adenocarcinomas. Among markers expected to stain adenocarcinoma, CEA stained 22 of 23 adenocarcinomas and, focally and very weakly, 4 mesotheliomas. CD15 stained all adenocarcinomas and, focally, 2 mesotheliomas. Cytokeratins stained both tumor types. The authors concluded that calretinin and thrombomodulin were the best positive mesothelioma markers and that CD15 and CEA were the most specific negative markers. 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: Retrospective laboratory study of diagnostic immunohistochemical staining on archived surgical tumor tissue
• Who was studied: Archived surgical tissue from 42 pleural epithelial mesotheliomas and 23 pulmonary adenocarcinomas, from the files of the Department of Human Pathology and Oncology, University of Florence, Italy. Dates of the cases are not given.
• Exposure: Not studied. The article tests diagnostic stains on tumor tissue and does not assess asbestos or other exposures.
• Main results:
  • Calretinin stained all 42 epithelial mesotheliomas.
  • Calretinin stained only 2 of 23 adenocarcinomas. The authors report sensitivity of 100% and specificity of 91.3% for calretinin.
  • Thrombomodulin stained 39 of 42 mesotheliomas and 5 (21.7%) of the adenocarcinomas, focally. Sensitivity was 92.9% and specificity 78.3%.
  • CD44H stained all 42 mesotheliomas.
  • CD44H also stained 13 (56.5%) of 23 adenocarcinomas, giving sensitivity of 100% and specificity of 43.5%.
  • HBME-1 stained 41 (97.6%) of 42 mesotheliomas.
  • HBME-1 also stained all adenocarcinomas, so it showed no specificity (0%).
  • In 4 mesotheliomas, CEA staining was focal and very weak. All but 1 of the 23 adenocarcinomas were CEA positive.
  • CD15 stained 2 mesotheliomas, focally, and all 23 adenocarcinomas.
  • The authors described CD15 as a highly specific marker for differentiating mesothelioma from adenocarcinoma.
  • Ber-EP4 stained 5 (11.9%) of 42 mesotheliomas, focally. It stained 22 (95.6%) of 23 adenocarcinomas strongly and diffusely.
  • B72.3 stained 6 mesotheliomas and 8 (34.7%) of 23 adenocarcinomas.
  • Cytokeratins AE1/AE3 and CAM5.2 stained all mesotheliomas and all adenocarcinomas. The authors considered them of no value for telling the two tumors apart.
  • EMA stained nearly all cases of both tumor types, but the staining patterns differed between them.
• The authors' conclusion: The authors concluded that calretinin and thrombomodulin are the best positive markers for mesothelial cells. They proposed a limited first panel of calretinin, thrombomodulin, CD15 and CEA, with CD15 and CEA as the most specific negative markers for separating mesothelioma from adenocarcinoma.

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: Calretinin, Mesothelioma, Adenocarcinoma, Lung Adenocarcinoma, Pleura, Monoclonal Antibody, HBME-1, CAM5.2.

Related studies

• Immunohistochemical panels for differentiating epithelial malignant mesothelioma from lung adenocarcinoma: a study with logistic regression analysis — R. Carella, G. Deleonardi, 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)
• 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)
• Value of the mesothelium-associated antibodies thrombomodulin, cytokeratin 5/6, calretinin, and CD44H in distinguishing epithelioid pleural mesothelioma from adenocarcinoma metastatic to the pleura — P.M. Cury, D.N. Butcher, et al. (2000)
• 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)
• Immunohistochemical analysis still has a limited role in the diagnosis of malignant mesothelioma. A study of thirteen antibodies — F. Roberts, C.M. Harper, et al. (2001)

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