Claudin 3, 4, and 15 expression in solid tumors of lung adenocarcinoma versus malignant pleural mesothelioma

Our plain-English summary of Claudin 3, 4, and 15 expression in solid tumors of lung adenocarcinoma versus malignant pleural mesothelioma, by S. Chaouche-Mazouni, A. Scherpereel, R. Zaamoum, et al (Annals of Diagnostic Pathology, 2015).

The study

• Authors: S. Chaouche-Mazouni, A. Scherpereel, R. Zaamoum, A. Mihalache, Z.C. Amir, N. Lebaïli, B. Delaire, P. Gosset
• Journal: Annals of Diagnostic Pathology
• Published: 2015;19(4):193-7
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Epithelioid malignant pleural mesothelioma (MPM) can easily be confused with lung adenocarcinomas (ACAs). In serous effusion, claudin (cldn) 3 is shown to be useful in the diagnosis of mesothelioma vs ACAs. Cldn15 is reported to be overexpressed in epithelioid mesothelioma and absent in human airway epithelium. The aim was to assess the value of cldn3 and cldn4 compared to that of BerEp4 and thyroid transcription factor-1 (TTF1) in differentiating lung ACA from epithelioid MPM and to examine the expression of cldn15 in these tumors. The expression of cldn3, cldn4, cldn15, BerEp4, and TTF1 was examined by immunohistochemistry in a total of 62 human specimen including 28 epithelioid MPMs and 34 ACAs of the lung. In lung ACA, cldn4 was strongly expressed in all 34 (100%) specimens followed by cldn3 in 33 (97%) of 34. BerEp4 was expressed in 32 (94.1%) of 34. TTF1 reacted for only 20 (58.82%) of 34 cases of lung ACA. In MPM specimens, the expression of cldn3 and4 as well as that of TTF1 was completely absent. In contrast, BerEp4 was focally expressed in 5 (17.85%) of 28 cases of epithelioid MPM. Cldn15 was strongly expressed in 53% pf epithelioid MPMs but also in 50% of lung ACAs. Its expression was moderate in normal pleura and limited in normal lung. Cldn3 and cldn4 appear to be the best performing carcinoma markers in discriminating lung ACA from mesothelioma compared with BerEp4 and TTF1. There is no differential expression of cldn15 between the 2 pathologies. However, the limited cldn15 expression in normal tissues and high expression in tumors make it an attractive candidate for cancer therapy.

Copyright © 2015 Elsevier Inc. All rights reserved.

In plain English

This laboratory study examined whether certain proteins, made visible by staining tissue, can help pathologists tell epithelioid malignant pleural mesothelioma apart from lung adenocarcinoma, two cancers the authors say can easily be confused. The authors stained 62 surgical specimens from two Algerian hospitals, 28 epithelioid mesotheliomas and 34 lung adenocarcinomas, plus normal tissues. They tested for claudin 3, claudin 4 and claudin 15, and for two markers already in use, BerEp4 and TTF1. Claudin 4 was found in all 34 lung adenocarcinomas and claudin 3 in 33 of 34. Neither was found in any mesothelioma. BerEp4 was found in 32 of 34 adenocarcinomas, but also, in patches, in 5 of 28 mesotheliomas. TTF1 was absent in the mesotheliomas but present in only 20 of 34 adenocarcinomas. Claudin 15 was found in 53% of mesotheliomas and 50% of adenocarcinomas. The authors concluded that claudins 3 and 4 performed best at telling the two cancers apart and that claudin 15 did not. They suggested claudin 15 could be a possible treatment target. The article does not discuss asbestos exposure.

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 diagnostic study using immunohistochemistry (tissue staining) on tumor specimens
• Who was studied: 62 surgical resection specimens from the CHU of Mustapha Pacha (Algiers) and the Public Hospital of Blida, Algeria: 28 epithelioid malignant pleural mesotheliomas and 34 lung adenocarcinomas, plus normal control tissues (colon, pleura, bronchi, bronchioles); dates not given
• Exposure: Asbestos exposure was not studied or reported. The study compared tissue markers (claudin 3, claudin 4, claudin 15, BerEp4, TTF1) between tumor types.
• Main results:
  • In lung adenocarcinomas, claudin 4 was strongly expressed in all 34 (100%) and claudin 3 in 33 (97%) of 34
  • In lung adenocarcinomas, BerEp4 was expressed in 32 (94.1%) of 34 and TTF1 in only 20 (58.82%) of 34
  • In epithelioid mesothelioma specimens, claudin 3, claudin 4 and TTF1 were completely absent
  • BerEp4 focally stained 5 (17.85%) of 28 epithelioid mesotheliomas
  • Claudin 15 was highly expressed in 53% of epithelioid mesotheliomas (15 of 28 in Table 2) and in 50% of lung adenocarcinomas (17 of 34 in Table 2)
  • In normal tissues, claudin 15 expression was moderate in normal pleura and limited in normal lung
• The authors' conclusion: The authors concluded that claudin 3 and claudin 4 appear to be the best-performing carcinoma markers for distinguishing lung adenocarcinoma from mesothelioma, compared with BerEp4 and TTF1. They found that the claudin 15 antibody used showed no diagnostic value for this distinction. They suggested that limited claudin 15 in normal tissue and high levels in tumors make it a possible candidate for cancer therapy.
• Limitations the authors state:
  • For TTF1-negative cases, lung origin rested on clinical and pathological correlation. The authors note that whether the adenocarcinomas were primary or secondary was not central to the study.

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: Lung Adenocarcinoma, Pleural Mesothelioma, Epithelioid, Mesothelioma, Epithelium, Thyroid Transcription Factor-1 (TTF-1), Immunohistochemistry, Pleura.

Related studies

• Utility of Claudin-4 versus BerEP4 and B72.3 in pleural fluids with metastatic lung adenocarcinoma — A. Patel, A.C. Borczuk, et al. (2020)
• Claudin-4 immunohistochemistry is highly effective in distinguishing adenocarcinoma from malignant mesothelioma in effusion cytology — V.Y. Jo, E.S. Cibas, et al. (2014)
• HBME-1, MOC-31, WT1 and calretinin: an assessment of recently described markers for mesothelioma and adenocarcinoma — J. Oates, C. Edwards (2000)
• Immunohistochemical panels for differentiating epithelial malignant mesothelioma from lung adenocarcinoma: a study with logistic regression analysis — R. Carella, G. Deleonardi, et al. (2001)
• Comparative genetic analysis of a rare synchronous collision tumor composed of malignant pleural mesothelioma and primary pulmonary adenocarcinoma — T. Naka, Y. Hatanaka, et al. (2016)
• Expression of thyroid transcription factor-1 in malignant pleural effusions — A. Khoor, A.L. Byrd-Gloster, et al. (2011)

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