Frequent expression of conventional endothelial markers in pleural mesothelioma: usefulness of claudin-5 as well as combined traditional markers to distinguish mesothelioma from angiosarcoma

Our plain-English summary of Frequent expression of conventional endothelial markers in pleural mesothelioma: usefulness of claudin-5 as well as combined traditional markers to distinguish mesothelioma from angiosarcoma, by Y. Nakashima, K. Inamura, H. Ninomiya, et al (Lung Cancer, 2020).

The study

• Authors: Y. Nakashima, K. Inamura, H. Ninomiya, S. Okumura, M. Mun, S. Kirimura, M. Kobayashi, K. Okubo, Y. Ishikawa
• Journal: Lung Cancer
• Published: 2020;148:20-27
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: Distinguishing pleural sarcomatoid mesotheliomas from true sarcomas is challenging because the former does not always express the mesothelial markers, and diagnosis is often made on the basis of keratin expression. Consequently, sarcomas such as angiosarcomas that express keratin complicate the differential diagnosis. Furthermore, some mesotheliomas have been reported to express endothelial markers. The aim of this study is to identify useful markers for distinguishing pleural sarcomatoid mesothelioma from angiosarcoma.

Materials And Methods: This study enrolled 147 patients with pleural mesothelioma-93 with epithelioid, 25 with biphasic, and 29 with sarcomatoid subtypes-and 41 patients with angiosarcomas in various organs. The expression levels of cytokeratin, mesothelial, and endothelial markers were assayed in both groups to identify the markers that could assist in distinguishing mesothelioma from angiosarcoma. Cytokeratin (AE1/AE3, CAM 5.2), endothelial (CD31, CD34, ERG, factor VIII, and claudin-5), and mesothelial (calretinin, WT-1, podoplanin (D2-40), EMA, and CK5/6) markers were immunohistochemically assayed using tissue blocks.

Results: More than 90% of the mesotheliomas and less than 20% of the angiosarcomas expressed cytokeratin. Calretinin was expressed in 82% of all types of mesotheliomas but in only 48% of sarcomatoid mesotheliomas. Endothelial markers were expressed in mesothelioma tissues-CD31 in 10.3%, CD34 in 3.5%, ERG in 29%, and factor VIII in 3.4%-and the positivity was higher in sarcomatoid than in epithelioid and biphasic mesotheliomas. Claudin-5 was expressed in all the angiosarcomas, but not in any of the mesotheliomas.

Conclusion: We found overlapping immunophenotypes in pleural mesotheliomas and angiosarcomas, but the sensitivity and specificity of claudin-5 expression were sufficient to distinguish between them. The differential diagnosis of mesothelioma should therefore include claudin-5 in a panel of immunohistochemical markers to distinguish mesothelioma from angiosarcoma.

Copyright © 2020 Elsevier B.V. All rights reserved.

In plain English

This laboratory study from Tokyo tested whether tissue stains can distinguish pleural mesothelioma from angiosarcoma, a similar-looking blood-vessel cancer. The authors stained tumor samples from 147 patients with pleural mesothelioma (93 epithelioid, 25 biphasic, 29 sarcomatoid) and 41 patients with angiosarcoma in various organs. Only one angiosarcoma started in the pleura. The keratin stain AE1/AE3 was positive in 143 of 147 mesotheliomas and 8 of 41 angiosarcomas, and CAM5.2 in 142 of 147 and 6 of 41. Calretinin, a standard mesothelioma marker, was positive in 120 of 146 mesotheliomas but in only 14 of 29 sarcomatoid mesotheliomas. Some blood-vessel markers also appeared in mesotheliomas, for example ERG in 39 of 134. Claudin-5 was found in none of 138 mesotheliomas and in all 36 angiosarcomas tested. The authors concluded that claudin-5 should be included in the stain panel used to separate the two cancers. They noted that only Japanese patients were studied and that some negative claudin-5 results could be false negatives. No angiosarcoma patient had a history of asbestos exposure; the article gave no exposure information for mesothelioma patients.

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 immunohistochemical (tissue staining) study comparing stored tumor samples of pleural mesothelioma and angiosarcoma
• Who was studied: The starting group was 165 consecutive pleural mesothelioma patients, taken from the Japanese Foundation for Cancer Research (JFCR) registry for 1992 to 2015 or treated at Tokyo Medical and Dental University from 2010 to 2018, plus 42 consecutive angiosarcoma patients from the JFCR registry for 1980 to 2018. After exclusions, the study analyzed 147 mesotheliomas (93 epithelioid, 25 biphasic, 29 sarcomatoid) and 41 angiosarcomas, one of which was pleural.
• Exposure: Not an asbestos exposure study. Tumors were stained for cytokeratins (AE1/AE3, CAM5.2), mesothelial markers (calretinin, WT-1, podoplanin (D2-40), EMA, CK5/6) and endothelial markers (CD31, CD34, ERG, factor VIII, claudin-5). The article stated that none of the angiosarcoma patients had a history of asbestos exposure. It gave no exposure information for the mesothelioma patients.
• Main results:
  • Keratin was positive in most mesotheliomas and few angiosarcomas. AE1/AE3 was positive in 143 of 147 mesotheliomas (97.3%) and 8 of 41 angiosarcomas (19.5%). CAM5.2 was positive in 142 of 147 mesotheliomas (96.6%) and 6 of 41 angiosarcomas (14.6%). The difference was statistically significant (p less than 0.001).
  • Calretinin was positive in 120 of 146 mesotheliomas (82.2%) and in none of 41 angiosarcomas. Among sarcomatoid mesotheliomas, it was positive in only 14 of 29 (48.3%).
  • Endothelial markers were found in some mesotheliomas: CD31 in 15 of 146 (10.3%), CD34 in 5 of 142 (3.5%), ERG in 39 of 134 (29.1%) and factor VIII in 5 of 146 (3.4%). ERG was positive in 14 of 25 sarcomatoid (56.0%), 11 of 21 biphasic (52.4%) and 14 of 88 epithelioid (15.9%) mesotheliomas.
  • Claudin-5 was positive in none of 138 mesotheliomas tested and in all 36 angiosarcomas tested. Eight sarcomatoid mesotheliomas showed several endothelial markers but were negative for claudin-5.
  • Absence of claudin-5 was the only marker with 100% sensitivity, specificity, positive and negative predictive values, and accuracy for distinguishing mesothelioma from angiosarcoma in this series.
• The authors' conclusion: The authors concluded that mesotheliomas and angiosarcomas showed overlapping staining patterns, that claudin-5 is a negative marker for mesothelioma, and that claudin-5 should be included in the panel of stains used to distinguish sarcomatoid mesothelioma from angiosarcoma.
• Limitations the authors state:
  • Errors in the final diagnosis of mesothelioma or angiosarcoma could not be completely ruled out.
  • Only one of the 41 angiosarcomas started in the pleura, and tumor origin may affect staining.
  • Epithelioid hemangioendothelioma, another vascular tumor that can resemble mesothelioma, was not studied.
  • Some negative claudin-5 results in mesotheliomas may have been false negatives, possibly because some specimens were too old to analyze.
  • Only Japanese patients were studied, which limits how far the results can be generalized.

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: Pleural Mesothelioma, Mesothelioma, Sarcomatoid, Sarcoma, Differential Diagnosis, Epithelioid, Biphasic Mesothelioma, CD34.

Related studies

• Primary pleural epithelioid angiosarcoma. A case report and review of the literature — E. Dainese, B. Pozzi, et al. (2010)
• Pseudomesotheliomatous angiosarcoma: a pleuropulmonary lesion simulating malignant pleural mesothelioma — G. Falconieri, R. Bussani, et al. (1997)
• Primary pleural angiosarcoma associated with pneumoconiosis: An autopsy case — K. Matsuda, T. Yamaryo, et al. (2015)
• Epithelioid angiosarcoma of the pleura: a case report — M.S. Roh, J.Y. Seo, et al. (2001)
• Angiosarcoma of the chest wall — T. Suzuki, S. Suzuki, et al. (1996)
• Usefulness of Claudin 4 in the cytological diagnosis of serosal effusions — S. Lonardi, C. Manera, et al. (2011)

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