Diagnostic utility of immunohistochemistry in distinguishing between epithelioid pleural mesotheliomas and breast carcinomas: a comparative study

Our plain-English summary of Diagnostic utility of immunohistochemistry in distinguishing between epithelioid pleural mesotheliomas and breast carcinomas: a comparative study, by N.G. Ordóñez, A.A. Sahin (Human Pathology, 2014).

The study

• Authors: N.G. Ordóñez, A.A. Sahin
• Journal: Human Pathology
• Published: 2014;45(7):1529-40
• Cited by: 56 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Epithelioid mesotheliomas and breast carcinomas can present a variety of morphologic patterns. Because of this, breast carcinomas that metastasize to the pleura and lung may be confused with mesotheliomas. The aim of the present study is to compare the immunohistochemical markers currently available for the diagnosis of these 2 malignancies and to determine the best panel of markers that can be used to assist in discriminating between them. Sixty epithelioid mesotheliomas and 80 breast carcinomas (40 triple negative and 40 estrogen receptor positive) were investigated for expression of the positive mesothelioma markers calretinin, keratin 5/6, mesothelin, podoplanin, thrombomodulin, and WT1; the positive carcinoma marker claudin 4; and the breast-associated markers gross cystic disease fluid protein 15 (GCDFP-15), mammaglobin, and GATA3. All of the epithelioid mesotheliomas reacted for calretinin and keratin 5/6, 93% for WT1; 88% for podoplanin; 77% for thrombomodulin; 23% for GATA3; and 0% for claudin 4, GCDFP-15, and mammaglobin, respectively. Of the triple-negative breast carcinomas, 100% expressed claudin 4; 5%, keratin 5/6; 30%, GATA3; 18%, mammaglobin; 15%, GCDFP-15; 56%, mesothelin; 38%, calretinin; 18%, thrombomodulin; 5%, WT1; and 3%, podoplanin. Among the estrogen receptor-positive breast carcinomas, 100% were claudin 4 and GATA3 positive; 70% expressed GCDFP-15; 63%, mammaglobin; 13%, calretinin; 13%, thrombomodulin; 8%, WT1; 5%, keratin 5/6; 3%, mesothelin; and 0%, podoplanin. It is concluded that podoplanin and WT1 are the best positive mesothelioma markers for differentiating epithelioid mesotheliomas from breast carcinomas. An accurate differential diagnosis can be reached with the use of these two markers in combination with the breast-associated markers GCDFP-15, mammaglobin, and GATA3.

Copyright © 2014 Elsevier Inc. All rights reserved.

In plain English

This laboratory study compared tumor tissue to find stains that help pathologists tell epithelioid pleural mesothelioma apart from breast cancer that has spread to the pleura and lung. The authors tested archived samples from 60 epithelioid pleural mesotheliomas and 80 invasive breast carcinomas (40 triple-negative and 40 estrogen receptor (ER)-positive) for ten immunohistochemical markers. Asbestos exposure was not studied. All 60 mesotheliomas stained for calretinin, keratin 5/6 and mesothelin. Many triple-negative breast cancers stained for these markers too (38%, 65% and 53%). Podoplanin stained 88% of mesotheliomas but only 1 triple-negative and no ER-positive breast cancer. WT1 stained 93% of mesotheliomas but only 5 breast cancers, and all 5 of those breast cancers stained only focally (the lowest grade, 1+). Claudin 4 stained every breast cancer and no mesothelioma. GCDFP-15 and mammaglobin stained no mesotheliomas, while GATA3 stained one-third of them. The authors concluded that podoplanin and WT1 were the best mesothelioma markers for this distinction. They also concluded that combining these two with GCDFP-15, mammaglobin and GATA3 usually makes it possible to tell the two cancers apart.

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: Comparative immunohistochemical study of archived tumor tissue from one institution's pathology files
• Who was studied: 60 epithelioid pleural mesotheliomas and 80 invasive breast carcinomas (40 triple-negative, 40 ER-positive) from The University of Texas MD Anderson Cancer Center, Houston; dates not given
• Exposure: No asbestos or other environmental exposure was studied. The tissue was tested for mesothelioma markers (calretinin, keratin 5/6, mesothelin, podoplanin, thrombomodulin, WT1), the carcinoma marker claudin 4, and the breast-associated markers GCDFP-15, mammaglobin and GATA3
• Main results:
  • All 60 mesotheliomas (100%) were positive for calretinin.
  • All 60 mesotheliomas were positive for keratin 5/6.
  • All 60 mesotheliomas were positive for mesothelin.
  • Calretinin was positive in 15 (38%) of the 40 triple-negative breast carcinomas.
  • Calretinin was positive, focally, in 5 of the ER-positive breast carcinomas.
  • Keratin 5/6 was positive in 26 (65%) of the triple-negative breast carcinomas.
  • Keratin 5/6 was positive in 2 (5%) of the ER-positive breast carcinomas.
  • Mesothelin was positive in 21 (53%) of the triple-negative breast carcinomas.
  • Mesothelin was positive in only 1 ER-positive breast carcinoma.
  • Podoplanin was positive in 53 (88%) of the mesotheliomas.
  • Podoplanin was positive in only 1 (3%) of the triple-negative breast carcinomas, focally, and in none of the ER-positive breast carcinomas.
  • WT1 was positive in 56 (93%) of the mesotheliomas; in 43 of these the staining was strong and diffuse, and in the rest it was focal.
  • WT1 was positive in 2 (5%) of the triple-negative and 3 (8%) of the ER-positive breast carcinomas. In all 5 of these breast carcinomas the staining was focal, graded 1+ (the lowest grade, meaning 1% to 25% of cells reacted).
  • Thrombomodulin was positive in 46 (77%) of the 60 mesotheliomas.
  • Thrombomodulin was positive in 7 (18%) of the triple-negative and 5 (13%) of the ER-positive breast carcinomas.
  • Claudin 4 was positive in all triple-negative and all ER-positive breast carcinomas.
  • Claudin 4 was positive in none of the mesotheliomas.
  • GCDFP-15 was positive in 28 (70%) of the ER-positive and 6 (15%) of the triple-negative breast carcinomas.
  • GCDFP-15 was positive in none of the mesotheliomas.
  • Mammaglobin was positive in 7 (18%) of the triple-negative breast carcinomas.
  • Mammaglobin was positive in 25 (63%) of the 40 ER-positive breast carcinomas.
  • Mammaglobin was positive in none of the mesotheliomas.
  • GATA3 was positive in all ER-positive breast carcinomas.
  • GATA3 was positive in only 30% of the triple-negative breast carcinomas.
  • GATA3 was positive in one-third of the mesotheliomas (20 of 60 in Table 2).
  • Because calretinin, mesothelin and keratin 5/6 were positive in all mesotheliomas and in many triple-negative breast carcinomas, the authors found these markers of no use for telling the two tumors apart.
• The authors' conclusion: The authors concluded that podoplanin and WT1 are the best positive mesothelioma markers for distinguishing epithelioid mesotheliomas from breast carcinomas. They concluded that a panel combining these two with GCDFP-15, mammaglobin and GATA3 usually makes it possible to distinguish epithelioid pleural mesotheliomas from metastatic breast carcinomas.

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: Immunohistochemistry, Epithelioid, Pleural Mesothelioma, Carcinoma, Mesothelioma, Metastasis, Pleura, Calretinin.

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• Differential Diagnosis of Epithelioid Malignant Mesothelioma With Lung and Breast Pleural Metastasis: A Systematic Review Compared With a Standardized Panel of Antibodies-A New Proposal That May Influence Pathologic Practice — N. Le Stang, L. Burke, et al. (2020)
• Utility and pitfalls of immunohistochemistry in the differential diagnosis between epithelioid mesothelioma and poorly differentiated lung squamous cell carcinoma — K. Kushitani, V.J. Amatya, et al. (2017)
• Value of PAX8, PAX2, napsin A, carbonic anhydrase IX, and claudin-4 immunostaining in distinguishing pleural epithelioid mesothelioma from metastatic renal cell carcinoma — N.G. Ordóñez (2013)
• GATA-3 and FOXA1 expression is useful to differentiate breast carcinoma from other carcinomas — D.G. Davis, M.T. Siddiqui, et al. (2016)

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