Value of the mesothelium-associated antibodies thrombomodulin, cytokeratin 5/6, calretinin, and CD44H in distinguishing epithelioid pleural mesothelioma from adenocarcinoma metastatic to the pleura

Our plain-English summary of Value of the mesothelium-associated antibodies thrombomodulin, cytokeratin 5/6, calretinin, and CD44H in distinguishing epithelioid pleural mesothelioma from adenocarcinoma metastatic to the pleura, by P.M. Cury, D.N. Butcher, C. Fisher, et al (Modern Pathology, 2000).

The study

• Authors: P.M. Cury, D.N. Butcher, C. Fisher, B. Corrin, A.G. Nicholson
• Journal: Modern Pathology
• Published: 2000;13(2):107-12
• Cited by: 128 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Until recently, the standard approach of most laboratories in distinguishing epithelioid pleural mesothelioma from metastatic adenocarcinoma has been a negative result from a panel of adenocarcinoma-associated antibodies. However, several "mesothelium-associated" antibodies have been proposed as useful in this situation, and we have applied four of these putative mesothelioma markers--thrombomodulin, cytokeratin 5/6, calretinin, and CD44H--to a series of 61 epithelioid pleural mesotheliomas and 63 metastatic adenocarcinomas with known primary sites (lung = 19; breast = 21; ovary = 6; colon = 10; kidney = 4; uterus, epididymis, pancreas = 1 case each). Of the mesotheliomas, 55 of 61 (90%) stained for thrombomodulin, 56 of 61 (92%) for cytokeratin 5/6, 47 of 51 cases (92%) were positive for calretinin, and 39 of 43 (91%) were positive for CD44H. Of the metastatic adenocarcinomas, 12 of 63 (19%) cases were positive for thrombomodulin, 9 of 63 (14%) were positive for CK5/6, and 27 of 60 (45%) were positive for CD44H. With calretinin, only 1 case of 59 (2%) showed positive nuclear staining. All four antibodies stained reactive mesothelium; thrombomodulin also stained endothelium; and CD44H variably stained lymphocytes, macrophages, and fibroblasts. We conclude that all four antibodies show high sensitivity for epithelioid mesothelioma, but only calretinin (98%), cytokeratin 5/6 (86%), and thrombomodulin (81%) show sufficient specificity for practical use in this situation.

In plain English

This laboratory study tested whether four antibody stains (thrombomodulin, cytokeratin 5/6, calretinin and CD44H) help pathologists tell epithelioid pleural mesothelioma apart from adenocarcinoma that has spread to the pleura from elsewhere in the body. The authors stained archived tissue from 61 epithelioid pleural mesotheliomas and 63 metastatic adenocarcinomas held by hospitals in London and Sao Paulo. The article does not discuss asbestos exposure. Among the mesotheliomas, 55 of 61 stained for thrombomodulin, 56 of 61 for cytokeratin 5/6, 47 of 51 for calretinin and 39 of 43 for CD44H. Among the adenocarcinomas, 12 of 63 stained for thrombomodulin, 9 of 63 for cytokeratin 5/6 and 27 of 60 for CD44H. For calretinin, 23 of 59 adenocarcinomas showed staining in the cell body, but only 1 of 59 showed staining in the cell nucleus. All four stains also marked reactive, non-malignant mesothelium. The authors concluded that the four stains had similar sensitivities and that nuclear calretinin staining was highly specific (98%). They judged cytokeratin 5/6 and thrombomodulin (81%) reasonably specific and CD44H insufficient for practical use. They noted that no stain was totally specific.

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 archived tumor tissue, assessing how well four antibodies distinguish epithelioid pleural mesothelioma from metastatic adenocarcinoma
• Who was studied: 61 cases of epithelioid pleural mesothelioma and 63 cases of metastatic adenocarcinoma, taken from the files of the Royal Brompton Hospital, London, and the Heart Institute and Clinical Hospital of the University of Sao Paulo, Brazil. The adenocarcinomas came from the breast (21), lung (19), colon (10), ovary (6), kidney (4), and epididymis, uterus and pancreas (1 each). The dates of the cases are not given. The mesothelioma diagnosis rested on negative histochemical and immunohistochemical staining in the correct clinical and radiologic context.
• Exposure: Not reported: the article does not describe asbestos or any other exposure of the patients. It tests antibody stains (thrombomodulin, cytokeratin 5/6, calretinin, CD44H) on tumor tissue.
• Main results:
  • Mesotheliomas, thrombomodulin: 55 of 61 (90%) stained positive
  • Mesotheliomas, cytokeratin 5/6: 56 of 61 (92%) stained positive
  • Mesotheliomas: 39 of 43 (91%) stained positive for CD44H and 47 of 51 (92%) for calretinin
  • Metastatic adenocarcinomas: 12 of 63 (19%) stained positive for thrombomodulin and 9 of 63 (14%) for cytokeratin 5/6
  • Metastatic adenocarcinomas, calretinin: 23 of 59 (39%) showed weak to moderate cytoplasmic staining, but only 1 of 59 (2%) showed nuclear staining
  • Calretinin specificity rose from 61% to 98% when only nuclear staining was counted
  • Thrombomodulin: sensitivity 90%, specificity 81%. Positive adenocarcinomas were mostly of lung origin (7 of 19) or kidney origin (2 of 4).
  • Cytokeratin 5/6: sensitivity 92%, specificity 86%
  • CD44H: sensitivity 91% but specificity only 55%, with positive staining in adenocarcinomas from all sites
  • All four antibodies also stained reactive mesothelium
• The authors' conclusion: The authors concluded that all four antibodies had similar sensitivities (90 to 92%) and that nuclear staining for calretinin (98%) showed high specificity. They judged cytokeratin 5/6 and thrombomodulin (81%) reasonably specific and CD44H (52%) insufficient for practical use. They added that cytokeratin 5/6 is somewhat easier to assess than thrombomodulin.
• Limitations the authors state:
  • Because the antibodies also stain reactive mesothelium, they do not separate mesothelioma from reactive (non-malignant) mesothelial hyperplasia
  • The study compared mesothelioma only with adenocarcinoma, not with other types of carcinoma
  • None of the antibodies is totally specific; results should be judged only alongside the clinical and routine pathology features
  • CD44H also stains lymphocytes, macrophages and fibroblasts, which makes assessment difficult in some specimens

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelium, Cytokeratin 5/6, Calretinin, Epithelioid, Pleural Mesothelioma, Adenocarcinoma, Pleura, Mesothelioma.

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• 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)
• 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)
• Expression of calretinin, thrombomodulin, keratin 5, and mesothelin in lung carcinomas of different types: an immunohistochemical analysis of 596 tumors in comparison with epithelioid mesotheliomas of the pleura — M. Miettinen, M. Sarlomo-Rikala (2003)
• 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)

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