The value of 'mesothelium-associated' antibodies in distinguishing between metastatic renal cell carcinomas and mesotheliomas

Our plain-English summary of The value of 'mesothelium-associated' antibodies in distinguishing between metastatic renal cell carcinomas and mesotheliomas, by M. Osborn, N. Pelling, M.M. Walker, et al (Histopathology, 2002).

The study

• Authors: M. Osborn, N. Pelling, M.M. Walker, C. Fisher, A.G. Nicholson
• Journal: Histopathology
• Published: 2002;41(4):301-7
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aims: Despite increasing usage of mesothelium-associated antibodies in diagnosis, a meta-analysis of studies analysing these antibodies in relation to distinguishing mesothelioma from renal cell carcinoma shows a paucity of published data. Given the clinical importance of elucidating this differential diagnosis, we compared the phenotypes of these two tumours using a panel of antibodies comprising recently described 'mesothelium-associated' antibodies and the more established 'epithelium-associated' antibodies.

Methods And Results: We applied an antibody panel comprising calretinin, cytokeratin (CK)5/6, thrombomodulin, carcinoembryonic antigen (CEA), BerEP4 and BCA225 to 37 cases of pleural mesotheliomas and 40 cases of renal cell carcinoma (27 primary tumours and 13 metastatic to the pleura). All mesotheliomas were either purely epithelioid or of mixed type. Cases of renal cell carcinoma were graded and classified as to cell type and architecture. For mesotheliomas, 0% stained for CEA, 16% for BerEP4, 83% for BCA225, 78% for CK5/6, 86% for thrombomodulin and 97% showed nuclear staining for calretinin. For renal cell carcinomas, 0% stained for CEA, 50% for BerEP4, 88% for BCA225, 5% for CK5/6, 32% for thrombomodulin and 10% showed nuclear staining for calretinin.

Conclusion: Calretinin, CK5/6 and BerEP4 appear the most useful antibodies in helping to distinguish between renal cell carcinomas and mesotheliomas, although BerEP4 was not particularly sensitive for renal cell carcinomas. Thrombomodulin was not as specific as the other 'mesothelium-associated' antibodies in this study, reflecting how staining for mesothelium-associated antibodies varies in carcinomas from different primary sites, and such variations should be taken into account when assessing the differential diagnosis of mesothelioma. In cases where doubt remains over distinguishing metastatic renal cell carcinoma from mesothelioma, data from such a panel should be viewed with caution and assessed in association with clinical, imaging and morphological features.

In plain English

This laboratory study tested whether antibody stains could help pathologists tell pleural mesothelioma from renal cell carcinoma (kidney cancer), which can spread to the pleura. The authors stained archived samples of 37 pleural mesotheliomas and 40 renal cell carcinomas (27 primary, 13 spread to the lung and pleura) from three London hospitals. Among the mesotheliomas, 36 of 37 (97%) stained for calretinin, 32 of 37 (86%) for thrombomodulin, 29 of 37 (78%) for CK5/6, 30 of 36 (83%) for BCA225, six of 37 (16%) for BerEP4 and none for CEA. Among the renal cell carcinomas, four of 40 (10%) showed nuclear calretinin staining, two of 40 (5%) stained for CK5/6, 13 of 40 (32%) for thrombomodulin, 20 of 40 (50%) for BerEP4, 35 of 40 (88%) for BCA225 and none for CEA. The authors concluded that calretinin, CK5/6 and BerEP4 appeared most useful, although BerEP4 was not particularly sensitive for renal cell carcinomas. They noted no antibody was 100% specific and advised judging doubtful cases alongside clinical, imaging and microscopic findings. The article did not address 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 immunohistochemistry study of archived tumour samples, comparing antibody staining patterns in two tumour types
• Who was studied: 37 cases of pleural mesothelioma (31 purely epithelioid, six biphasic) and 40 cases of renal cell carcinoma (27 primary tumours, 13 metastases to the lung and pleura), from the archives of the Royal Brompton, Royal Marsden and St Mary's Hospitals, London
• Main results:
  • Mesotheliomas: none of 37 stained for CEA
  • Mesotheliomas: 32 of 37 (86%) were positive for thrombomodulin and 36 of 37 (97%) for calretinin
  • Mesotheliomas: 30 of 36 (83%) were positive for BCA225 and 29 of 37 (78%) for CK5/6
  • Renal cell carcinomas: 20 of 40 (50%) were positive for BerEP4 and 35 of 40 (88%) for BCA225
  • Renal cell carcinomas: 2 of 40 (5%) were positive for CK5/6, 13 of 40 (32%) for thrombomodulin, and 4 of 40 (10%) showed predominantly nuclear calretinin staining
  • Renal cell carcinomas: a further 6 of 40 showed cytoplasmic-only calretinin staining
  • Among the renal cell carcinomas, positive staining for mesothelium-associated antibodies showed no obvious link to tumour variant or nuclear grade
  • The authors reported a specificity for mesothelioma of 93% for CK5/6 and 88% for nuclear calretinin staining in this comparison
  • Thrombomodulin specificity for mesothelioma in this study was 68%
  • BerEP4 had low sensitivity for renal cell carcinomas (50%). The authors said that a positive result argues against mesothelioma, but a negative result does not appear of much value.
  • BCA225 sensitivity for renal cell carcinomas was reported as 90%, with a specificity of 17%
• The authors' conclusion: The authors concluded that a panel of calretinin, CK5/6 and BerEP4 appeared most useful for helping distinguish renal cell carcinoma from mesothelioma, although BerEP4 was not particularly sensitive for renal cell carcinomas. They found thrombomodulin less specific, and staining for BCA225 and CEA of no use. In doubtful cases, they advised viewing panel results with caution alongside clinical, imaging and morphological features.
• Limitations the authors state:
  • No antibody tested was 100% specific
  • The authors could not explain why thrombomodulin specificity was lower than in a previous study using similar antibody and dilutions

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelium, Carcinoma, Mesothelioma, Meta-Analysis, Differential Diagnosis, Epithelium, Calretinin, Carcinoembryonic Antigen (CEA).

Related studies

• 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)
• Value of the mesothelium-associated antibodies thrombomodulin, cytokeratin 5/6, calretinin, and CD44H in distinguishing epithelioid pleural mesothelioma from adenocarcinoma metastatic to the pleura — P.M. Cury, D.N. Butcher, et al. (2000)
• 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)
• 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)
• Cystic renal cell carcinoma: arose as a simple cyst, recurred repeatedly as a multicystic mass and finally presented as a solid mass — Y. Shishikura, M. Furusato, et al. (1998)

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