Application of immunohistochemistry in the diagnosis of epithelioid mesothelioma: a review and update

Our plain-English summary of Application of immunohistochemistry in the diagnosis of epithelioid mesothelioma: a review and update, by N.G. Ordóñez (Human Pathology, 2013).

The study

• Author: N.G. Ordóñez
• Journal: Human Pathology
• Published: 2013;44(1):1-19
• Type of article: Review
• Cited by: 56 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

A large number of immunohistochemical markers that can assist in the differential diagnosis of epithelioid mesotheliomas are currently available. Because these markers are expressed differently in the various types of carcinomas that can metastasize to the serosal membranes and can potentially be confused with epithelioid mesothelioma, their selection for inclusion in a diagnostic panel largely depends on the differential diagnosis, as well as on which ones work the best in a given laboratory. Traditionally, the panels used in the differential diagnosis of epithelioid mesothelioma have consisted of a combination of positive mesothelioma markers and broad-spectrum carcinoma markers. At present, a wide variety of organ-associated carcinoma markers such as thyroid transcription factor-1 and napsin A for the lung, PAX 8 and PAX 2 for the kidney, and Müllerian-derived tumors; gross cystic disease fluid protein-15 and mammaglobin for the breast; and CDX2 for intestinal differentiation are available, which can assist in establishing the site of origin of an adenocarcinoma when included in a diagnostic panel. This article provides updated information on the composition of the panels of markers recommended in the various differential diagnoses.

Copyright © 2013 Elsevier Inc. All rights reserved.

In plain English

This article was a review, by a single author at The University of Texas MD Anderson Cancer Center, of immunohistochemical markers (laboratory stains applied to tissue). These markers are used to tell epithelioid mesothelioma apart from carcinomas that spread to the serosal membranes, the linings of the chest and abdomen. It did not study asbestos exposure. The author grouped the markers into four kinds and summarized published staining rates for each, including rates from the author's own earlier studies. The recommended marker panels differed by the tumor being ruled out. Against lung adenocarcinoma, calretinin, keratins 5 or 5/6, podoplanin and WT1 were named the best positive mesothelioma markers. For peritoneal mesothelioma versus serous carcinoma, MOC-31, Ber-EP4, ER and PAX 8 were named the best carcinoma markers. HBME-1 and h-caldesmon were judged not useful, and several newer markers had too few studies to judge. The author concluded that no available marker was absolutely specific and sensitive for epithelioid mesothelioma. The choice of markers depends on the tumor's location and appearance, the patient's sex and the clinical findings.

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: Narrative review of published literature on immunohistochemical markers (single author)
• Who was studied: No patient population. Published studies on markers used to distinguish epithelioid mesothelioma from carcinomas metastatic to the serosal membranes, grouped into four marker categories
• Exposure: Not addressed. The review concerns diagnostic tissue staining markers, not asbestos or fiber exposure
• Main results:
  • Calretinin was described as the most commonly used positive mesothelioma marker. Its reported expression in epithelioid mesotheliomas in published studies ranged from about 55% to 100% of cases.
  • For epithelioid mesothelioma versus lung adenocarcinoma, the best positive mesothelioma markers were calretinin, keratins 5 or 5/6, podoplanin and WT1. The best positive carcinoma markers were MOC-31, Ber-EP4, B72.3, BG-8, TTF-1 and napsin A.
  • For epithelioid mesothelioma versus squamous cell carcinoma, the best positive carcinoma markers were MOC-31, Ber-EP4, CEA, BG8 and p63. WT1 was named the best positive mesothelioma marker.
  • For epithelioid peritoneal mesothelioma versus serous carcinoma of the ovary and peritoneum, the best positive carcinoma markers were MOC-31, Ber-EP4, ER and PAX 8. Among positive mesothelioma markers, calretinin appeared most useful.
  • For epithelioid mesothelioma versus breast carcinoma, the best positive mesothelioma markers were WT1, podoplanin and mesothelin. The best carcinoma markers were MOC-31, Ber-EP4, BG-8, GCDFP-15 and mammaglobin.
  • For epithelioid mesothelioma versus renal cell carcinoma, the best positive mesothelioma markers were calretinin, podoplanin, keratin 5/6 and mesothelin. The most useful carcinoma markers were CD15, PAX 8, PAX 2 and RCC Ma.
  • h-Caldesmon was judged not useful because later investigations did not confirm early reports. HBME-1 was judged not useful because staining patterns overlapped.
  • Several newer markers (for example COL3A1 and MUC4) had too few or too small studies for their value to be determined.
• The authors' conclusion: The author concluded that, although many markers can assist in diagnosing epithelioid mesothelioma, none is absolutely specific and sensitive. Marker selection depends on tumor location and histologic features, patient sex and clinical findings, and also on which markers work best in a given laboratory.

Topics

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

Medical terms in this study, explained in our Lexicon: Immunohistochemistry, Epithelioid, Mesothelioma, Differential Diagnosis, Carcinoma, Metastasis, Thyroid Transcription Factor-1 (TTF-1), CDX2.

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• Diagnostic utility of immunohistochemistry in distinguishing between epithelioid pleural mesotheliomas and breast carcinomas: a comparative study — N.G. Ordóñez, A.A. Sahin (2014)
• 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)
• Immunohistochemistry: applications to the evaluation of lung and pleural neoplasms: part 2 — H. Mani, D.S. Zander (2012)
• Membranous HEG1 expression is a useful marker in the differential diagnosis of epithelioid and biphasic malignant mesothelioma versus carcinomas — K. Hiroshima, D. Wu, et al. (2021)

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