CD146 immunohistochemical staining for the separation of benign from malignant mesothelial proliferations

Our plain-English summary of CD146 immunohistochemical staining for the separation of benign from malignant mesothelial proliferations, by T. Salisbury, A. Churg (Virchows Archiv, 2021).

The study

• Authors: T. Salisbury, A. Churg
• Journal: Virchows Archiv
• Published: 2021;479(5):1047-1050
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The separation of benign from malignant mesothelial cells is often a challenging problem. Some studies have suggested that immunohistochemical staining of CD146 can be used to make this distinction, but there are marked differences in the reported results. Here, we assessed CD146 expression in tissue microarray specimens of 32 epithelioid reactive mesothelial hyperplasias, 17 spindle cell reactive mesothelial proliferations, 43 epithelioid mesotheliomas, and 31 sarcomatoid mesotheliomas. We found that, although the specificity of CD146 for epithelioid mesotheliomas versus reactive epithelial mesothelial proliferations was high (94%), staining intensity and extent was usually low and sensitivity was poor (23%). For sarcomatoid mesotheliomas versus reactive spindle cell mesothelial processes, both measures (33% sensitivity, 76% specificity) were inadequate. Furthermore, strong staining of endothelial cells and fibroblasts often created difficulties in interpretation. In comparison, BAP1 was lost in 21/43 (49%) epithelioid and 9/31 (29%) sarcomatoid mesotheliomas and methylthioadenosine phosphorylase (MTAP) was lost in 9/40 (23%) epithelioid and 7/29 (24%) sarcomatoid mesotheliomas from these TMAs. There was no association between CD146 staining and BAP1 or MTAP retention/loss. We conclude that CD146 staining is probably not useful for separating malignant from benign mesothelial proliferations.

© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

In plain English

This brief report from pathologists in Vancouver, Canada, tested whether a laboratory stain for the protein CD146 can help tell benign (reactive) mesothelial cell growths apart from mesothelioma. Earlier studies had disagreed on this question. The authors stained tissue microarrays (small tissue samples arranged together on slides) from 32 reactive epithelioid mesothelial hyperplasias, 17 reactive spindle cell mesothelial proliferations, 43 epithelioid mesotheliomas and 31 sarcomatoid mesotheliomas. The diagnoses were confirmed by follow-up. CD146 staining was seen in 10 of 43 (23%) epithelioid and 10 of 31 (33%) sarcomatoid mesotheliomas. It was also seen in 2 of 32 (6%) reactive epithelioid cases and 4 of 17 (24%) reactive spindle cell cases. Sensitivity and specificity were 23% and 94% for epithelioid mesothelioma, and 33% and 76% for sarcomatoid mesothelioma. Most positive mesotheliomas stained no more strongly than the reactive cases. Staining of blood vessels and fibroblasts made interpretation difficult. CD146 staining showed no association with loss of two other markers, BAP1 and MTAP. The authors concluded that CD146 staining is probably not useful for this distinction. Asbestos exposure was not examined.

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: Brief report: laboratory diagnostic study of immunohistochemical staining on tissue microarrays
• Who was studied: Tissue samples (duplicate cores on two tissue microarrays) from 32 reactive epithelioid mesothelial hyperplasias, 17 spindle cell reactive mesothelial proliferations, 43 epithelioid mesotheliomas and 31 sarcomatoid mesotheliomas, studied at the University of British Columbia and Vancouver General Hospital. Diagnoses were confirmed by follow-up. The article does not state dates or the body site of the tumors.
• Exposure: No asbestos or other exposure was studied. The study tested a diagnostic stain (anti-CD146 antibody EPR3208), compared with BAP1 and MTAP stains.
• Main results:
  • CD146 was expressed in 10 of 43 (23%) epithelioid mesotheliomas and 10 of 31 (33%) sarcomatoid mesotheliomas
  • CD146 was positive in 2 of 32 (6%) reactive epithelioid cases and 4 of 17 (24%) reactive spindle cell cases
  • Sensitivity/specificity was 23%/94% for epithelioid mesothelioma and 33%/76% for sarcomatoid mesothelioma. Most positive cases did not express CD146 more than the reactive proliferations did.
  • CD146 staining of normal endothelial cells (vessels) and fibroblasts created significant challenges in interpretation
  • In the mesotheliomas, BAP1 was lost in 21 of 43 (49%) epithelioid and 9 of 31 (29%) sarcomatoid cases. MTAP was lost in 9 of 40 (23%) epithelioid and 7 of 29 (24%) sarcomatoid cases. CD146 staining showed no correlation with loss or retention of either marker.
• The authors' conclusion: The authors concluded that CD146 staining is probably not useful for separating malignant from benign mesothelial proliferations, and probably adds no value to existing ancillary tests in the diagnostic workup of malignant mesothelioma.
• Limitations the authors state:
  • The authors note that using tissue microarrays rather than whole sections is a possible confounder

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, Mesothelial Cells, Epithelioid, Reactive Mesothelial Hyperplasia, Spindle Cell, Mesothelioma, Sarcomatoid, Fibroblast.

Related studies

• Cyclin D1 immunohistochemical staining to separate benign from malignant mesothelial proliferations — J. Pors, J. Naso, et al. (2020)
• Highlights of the 14th international mesothelioma interest group meeting: Pathologic separation of benign from malignant mesothelial proliferations and histologic/molecular analysis of malignant mesothelioma subtypes — A. Churg, K. Nabeshima, et al. (2018)
• IMP3 and GLUT-1 immunohistochemistry for distinguishing benign from malignant mesothelial proliferations — A.F. Lee, A.M. Gown, et al. (2013)
• The separation of benign and malignant mesothelial proliferations — A. Churg, F. Galateau-Salle (2012)
• Immunohistochemistry for NF2, LATS1/2, and YAP/TAZ Fails to Separate Benign From Malignant Mesothelial Proliferations — B.S. Sheffield, J. Lorette, et al. (2016)
• BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations — M. Cigognetti, S. Lonardi, et al. (2015)

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