Value of claudin-4 immunostaining in the diagnosis of mesothelioma

Our plain-English summary of Value of claudin-4 immunostaining in the diagnosis of mesothelioma, by N.G. Ordóñez (American Journal of Clinical Pathology, 2013).

The study

• Author: N.G. Ordóñez
• Journal: American Journal of Clinical Pathology
• Published: 2013;139(5):611-9
• Cited by: 48 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Claudin-4 (CL-4) is a tight junction-associated protein that is expressed in most epithelial cells but absent in mesothelial cells. The purpose of this study is to evaluate the utility of CL-4 immunostaining for assisting in the differential diagnosis of mesothelioma. Sixty mesotheliomas (40 epithelioid, 10 biphasic, and 10 sarcomatoid), 185 carcinomas of different origins that can potentially be confused with mesotheliomas, 37 soft-tissue sarcomas, and 5 melanomas were investigated for CL-4 expression. All 60 mesotheliomas were CL-4 negative. In contrast, 169 (91%) of 185 carcinomas expressed this marker. Five of 8 desmoplastic small round cell tumors and the epithelial component of all 5 biphasic synovial sarcomas were CL-4 positive, whereas none of the remaining soft-tissue sarcomas or melanomas expressed this marker. It is concluded that CL-4 is a highly specific and sensitive immunohistochemical marker for assisting in distinguishing epithelioid mesotheliomas from metastatic carcinomas to the serosal membranes.

In plain English

This single-author laboratory study tested whether claudin-4 staining helps tell mesothelioma apart from tumors resembling it. Claudin-4 is a protein present in most epithelial cells but absent in mesothelial cells. The article does not discuss asbestos exposure. Archived tissue from 60 mesotheliomas (40 epithelioid, 10 biphasic, 10 sarcomatoid), 185 carcinomas, 37 soft-tissue sarcomas and 5 melanomas was stained. None of the 60 mesotheliomas stained positive, but 169 (91%) of 185 carcinomas did. These included all lung, breast, pancreas, colon and prostate adenocarcinomas. Only 2 of 10 sarcomatoid lung carcinomas showed focal staining in spindle-cell areas. Five of 8 desmoplastic small round cell tumors and epithelial parts of all 5 biphasic synovial sarcomas were positive; other sarcomas and melanomas were negative. The author concluded that claudin-4 is a highly specific and sensitive marker for distinguishing epithelioid mesotheliomas from carcinomas that had spread to the serosal membranes. The author added that it does not appear to have significant value for separating sarcomatoid lung carcinomas from sarcomatoid mesotheliomas, but may help by revealing small epithelial areas not apparent on routine histology.

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 study of a diagnostic stain (immunohistochemistry) on archived tumor tissue. Cases with an unequivocal diagnosis of mesothelioma were selected and compared with other tumors that can be confused with mesothelioma.
• Who was studied: Tumor specimens from the files of the Department of Pathology, University of Texas M.D. Anderson Cancer Center: 60 mesotheliomas (40 epithelioid, 10 biphasic, 10 sarcomatoid), 185 carcinomas of different origins, 37 soft-tissue sarcomas and 5 melanomas. The article does not state the dates of the cases or whether the mesotheliomas were pleural or peritoneal.
• Exposure: No asbestos or other exposure was studied. The test examined was immunostaining for claudin-4 (CL-4) using the 3E2C1 mouse monoclonal antibody.
• Main results:
  • Mesotheliomas: none of the 60 (epithelioid, biphasic or sarcomatoid) were positive for claudin-4.
  • Carcinomas overall: 169 (91%) of 185 were positive for claudin-4.
  • All adenocarcinomas of the lung, pancreas, breast, colon and prostate were positive. So were 44 (98%) of 45 ovarian serous carcinomas (15 primary, 30 metastatic to the peritoneum).
  • Kidney cancers: 28 (85%) of 33 clear cell, 10 of 10 papillary and 12 of 12 chromophobe renal cell carcinomas were positive. Lung cancers: 19 (95%) of 20 squamous cell carcinomas and all 3 small cell carcinomas were positive.
  • Sarcomatoid lung carcinomas: only 2 of 10 showed staining, and only in small focal areas of the spindle cell component. The author judged that claudin-4 therefore does not appear to have significant value in distinguishing these tumors from sarcomatoid mesotheliomas.
  • The author qualified this: in tumors with small epithelial areas not apparent on routine histology, claudin-4 can help identify those areas, and may therefore help distinguish such tumors from sarcomatoid mesotheliomas.
  • Soft-tissue tumors: 5 of 8 desmoplastic small round cell tumors were positive. In all 5 biphasic synovial sarcomas, staining was limited to the epithelial component.
  • All 3 monophasic spindle cell synovial sarcomas, and the spindle cell component of the biphasic synovial sarcomas, were negative.
  • All solitary fibrous tumors of the pleura, malignant fibrous histiocytomas, angiosarcomas, leiomyosarcomas, rhabdomyosarcomas and melanomas were negative.
• The authors' conclusion: The author concluded that claudin-4 is a highly specific and sensitive marker for distinguishing epithelioid mesotheliomas from carcinomas that have spread to the serosal membranes, and recommended it as a primary marker in diagnostic panels. The author compared claudin-4 with other carcinoma markers (MOC-31, Ber-EP4, BG-8, TAG-72, CD15, CEA) using published studies; this study did not test those markers.

Topics

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

Medical terms in this study, explained in our Lexicon: Claudin-4, Mesothelioma, Mesothelial Cells, Differential Diagnosis, Epithelioid, Biphasic Mesothelioma, Sarcomatoid, Carcinoma.

Related studies

• Value of PAX8, PAX2, claudin-4, and h-caldesmon immunostaining in distinguishing peritoneal epithelioid mesotheliomas from serous carcinomas — N.G. Ordóñez (2013)
• 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)
• Claudin-4 immunohistochemistry is a useful pan-carcinoma marker for serous effusion specimens — M. Vojtek, M.D. Walsh, et al. (2019)
• The "Brescia panel" (Claudin-4 and BRCA-associated protein 1) in the differential diagnosis of mesotheliomas with epithelioid features versus metastatic carcinomas — L. Bernardi, T. Bizzarro, et al. (2021)
• Claudin-4 immunohistochemistry is highly effective in distinguishing adenocarcinoma from malignant mesothelioma in effusion cytology — V.Y. Jo, E.S. Cibas, et al. (2014)
• Value of thrombomodulin immunostaining in the diagnosis of mesothelioma — N.G. Ordóñez (1997)

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