Value of PAX8, PAX2, napsin A, carbonic anhydrase IX, and claudin-4 immunostaining in distinguishing pleural epithelioid mesothelioma from metastatic renal cell carcinoma

Our plain-English summary of Value of PAX8, PAX2, napsin A, carbonic anhydrase IX, and claudin-4 immunostaining in distinguishing pleural epithelioid mesothelioma from metastatic renal cell carcinoma, by N.G. Ordóñez (Modern Pathology, 2013).

The study

• Author: N.G. Ordóñez
• Journal: Modern Pathology
• Published: 2013;26(8):1132-43
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Both mesotheliomas and renal cell carcinomas can present a wide variety of cytomorphologic features and histologic patterns. Because of this, renal cell carcinomas metastatic to the pleura and lung can be confused with mesotheliomas. Recently, a variety of positive carcinoma markers, including kidney-associated markers, have become available. The aim of this study is to investigate the value of some of these markers, specifically PAX8, PAX2, napsin A, carbonic anhydrase IX, and claudin-4, for assisting in distinguishing pleural epithelioid mesotheliomas from metastatic renal cell carcinomas. To do so, a total of 40 pleural epithelioid mesotheliomas and 55 renal cell carcinomas (33 clear cell, 10 papillary, and 12 chromophobe) were investigated. In all, 91% of the renal cell carcinomas expressed claudin-4, 89% PAX8, 60% PAX2, 71% carbonic anhydrase IX, and 29% napsin A. All of the mesotheliomas were positive for carbonic anhydrase IX and were negative for all of the other markers. On the basis of these results, it is concluded that claudin-4 and PAX8 have a higher sensitivity and specificity for assisting in discriminating between pleural epithelioid mesotheliomas and renal cell carcinomas when compared with all of the other positive carcinoma markers that are, at present, recommended to be included in the immunohistochemical panels used in this differential diagnosis. Even though PAX2 and napsin A are highly specific, because of their low sensitivity, they have only a limited value. Carbonic anhydrase IX is not useful.

In plain English

This laboratory study, by a single author at The University of Texas MD Anderson Cancer Center in Houston, tested whether five tissue stains could help pathologists tell pleural epithelioid mesothelioma apart from kidney cancer (renal cell carcinoma) that has spread to the chest. Stored tissue from 40 pleural epithelioid mesotheliomas and 55 renal cell carcinomas (33 clear cell, 10 papillary and 12 chromophobe) was stained. None of the 40 mesotheliomas stained for PAX8, PAX2, napsin A or claudin-4. Among the kidney cancers, 91% stained for claudin-4, 89% for PAX8 and 60% (33 of 55) for PAX2. Napsin A stained 8 of 33 clear cell and 7 of 10 papillary tumors and none of the chromophobe tumors. Carbonic anhydrase IX stained all 40 mesotheliomas and 39 of the 55 kidney cancers. The author concluded that claudin-4 and PAX8 were the best of these markers. PAX2 and napsin A had limited value because they missed many kidney cancers, and carbonic anhydrase IX was not useful. The study did not look at 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: Diagnostic laboratory (immunohistochemistry) study of stored tissue samples, comparing staining patterns in two tumor types
• Who was studied: Tissue from 40 pleural epithelioid mesotheliomas and 55 renal cell carcinomas, taken from the pathology files of The University of Texas MD Anderson Cancer Center, Houston, TX. The renal cell carcinomas were 33 clear cell (22 metastatic, 11 primary), 10 papillary and 12 chromophobe. The article gives no dates for the cases.
• Exposure: No asbestos exposure was assessed. What was tested was staining of the tissue with five markers: PAX8, PAX2, napsin A, carbonic anhydrase IX and claudin-4.
• Main results:
  • PAX8: the text reports 49 (89%) of 55 renal cell carcinomas positive. By subtype, 31 (94%) of 33 clear cell, 10 (100%) of 10 papillary and 9 (75%) of 12 chromophobe were positive. All 40 mesotheliomas were negative.
  • PAX2: 33 (60%) of 55 renal cell carcinomas were positive. None of the mesotheliomas were positive.
  • Napsin A: 8 (24%) of 33 clear cell and 7 (70%) of 10 papillary renal cell carcinomas were positive. None of the 12 chromophobe tumors and none of the mesotheliomas were positive.
  • Carbonic anhydrase IX: 32 (97%) of 33 clear cell and 7 (70%) of 10 papillary renal cell carcinomas were positive, but none of the 12 chromophobe tumors. All 40 epithelioid mesotheliomas were also positive, 28 of them with strong, diffuse staining.
  • Claudin-4: 28 (85%) of 33 clear cell, 10 of 10 papillary and 12 of 12 chromophobe renal cell carcinomas were positive (table total 50, 91%). None of the mesotheliomas were positive.
• The authors' conclusion: The author concluded that claudin-4 and PAX8 should be considered the best positive carcinoma markers for this distinction. PAX2 and napsin A have limited value because of their lower sensitivity, and carbonic anhydrase IX has no value because both tumor types commonly express it.

Topics

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

Medical terms in this study, explained in our Lexicon: Claudin-4, Epithelioid, Mesothelioma, Carcinoma, Pleura, Differential Diagnosis.

Related studies

• Carbonic anhydrase IX is expressed in mesothelioma and metastatic clear cell renal cell carcinoma of the lung — M.L. Ramsey, B.J. Yuh, et al. (2012)
• Value of PAX8, PAX2, claudin-4, and h-caldesmon immunostaining in distinguishing peritoneal epithelioid mesotheliomas from serous carcinomas — N.G. Ordóñez (2013)
• The value of 'mesothelium-associated' antibodies in distinguishing between metastatic renal cell carcinomas and mesotheliomas — M. Osborn, N. Pelling, et al. (2002)
• Carbonic anhydrase IX (CAIX) does not differentiate between benign and malignant mesothelium — V. Ananthanarayanan, M. Tretiakova, et al. (2014)
• Metastatic renal cell carcinoma mimicking pleural mesothelioma — D.R. Taylor, W. Page, et al. (1987)
• A comparative immunohistochemical study of malignant mesothelioma and renal cell carcinoma: the diagnostic utility of Leu-M1, Ber EP4, Tamm-Horsfall protein and thrombomodulin — R.L. Attanoos, H. Goddard, et al. (1995)

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