Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies

Our plain-English summary of Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies, by A.S. Abutaily, B.J. Addis, W.R. Roche (Journal of Clinical Pathology, 2002).

The study

• Authors: A.S. Abutaily, B.J. Addis, W.R. Roche
• Journal: Journal of Clinical Pathology
• Published: 2002;55(9):662-8
• Cited by: 92 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Aim: The value of immunohistochemical staining in differentiating between malignant mesothelioma and pulmonary adenocarcinoma was re-examined using newly available commercial antibodies, with the aim of increasing the sensitivity and specificity of diagnosis, and simplifying the antibody panel required.

Methods: Forty one malignant mesotheliomas and 35 lung adenocarcinomas were studied. Commercial antibodies to calretinin, E-cadherin, N-cadherin, surfactant apoprotein A (SP-A), thyroid transcription factor 1 (TTF-1), thrombomodulin, and cytokeratin 5/6 were applied using the streptavidin-biotin-peroxidase complex procedure on formalin fixed, paraffin wax embedded tissue.

Results: E-cadherin was expressed in all adenocarcinomas and in 22% of the mesotheliomas. TTF-1 expression was detected in 69% of the adenocarcinomas and none of the mesotheliomas. Positive staining with polyclonal anticalretinin was detected in 80% of the mesotheliomas and 6% of the adenocarcinomas. N-cadherin was expressed in 78% of mesotheliomas and 26% of adenocarcinomas. Thrombomodulin was expressed in 6% of the adenocarcinomas and in 53% of the mesotheliomas. Cytokeratin 5/6 expression was detected in 6% of the adenocarcinomas and 63% of the mesotheliomas. The results were compared with the standard laboratory panel for mesothelioma diagnosis: anticarcinoembryonic antigen (anti-CEA), LeuM1, BerEP4, and HBME-1.

Conclusion: Of the antibodies used in this study, E-cadherin was 100% sensitive for pulmonary adenocarcinoma and TTF-1 was 100% specific for pulmonary adenocarcinoma. The application of these two antibodies alone was adequate for the diagnosis of 69% of adenocarcinomas and 78% of mesotheliomas. Where TTF-1 is negative and E-cadherin is positive, a secondary panel of antibodies, including BerEP4 and LeuM1 (CD15) and antibodies directed against CEA, calretinin, cytokeratin 5/6, thrombomodulin, and N-cadherin, is required for differentiation between malignant mesothelioma and pulmonary adenocarcinoma.

In plain English

This laboratory study, based on archived tissue at Southampton General Hospital, tested whether newer antibody stains could help pathologists tell malignant mesothelioma apart from lung adenocarcinoma. The authors stained tissue from 41 malignant mesotheliomas (1990 to 1997) and 35 resected lung adenocarcinomas (1997 and 1998). The article does not report on asbestos exposure. E-cadherin stained all 35 adenocarcinomas and 22% of the mesotheliomas. TTF-1 stained 69% of the adenocarcinomas and none of the mesotheliomas. Among mesotheliomas, calretinin stained 80%, N-cadherin 78%, cytokeratin 5/6 63% and thrombomodulin 53%. Among adenocarcinomas, calretinin, cytokeratin 5/6 and thrombomodulin each stained 6%, and N-cadherin 26%. Tumours negative for both E-cadherin and TTF-1 accounted for 78% of mesotheliomas. Tumours that were E-cadherin positive but TTF-1 negative needed further stains. The authors concluded that E-cadherin and TTF-1 should be the first stains used. They noted that their choice of antibodies was not comprehensive, and that patchy thrombomodulin staining may have produced false negatives.

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 tissue comparing antibody stains
• Who was studied: 76 archived tumour specimens from Southampton General Hospital, UK: 41 open or thoracoscopic biopsies of malignant mesothelioma (11 epithelioid, 7 sarcomatoid, 23 mixed) from 1990 to 1997, and 35 sequential resected primary pulmonary adenocarcinomas from 1997 and 1998
• Exposure: Not studied. The article reports no asbestos or other exposure data. It tested antibody stains on tumour tissue.
• Main results:
  • All 35 adenocarcinomas stained for E-cadherin (and for SP-A)
  • Among the 41 mesotheliomas, none stained for TTF-1 or LeuM1, 2% for CEA, 7% for BerEP4, and 22% for E-cadherin
  • TTF-1 was 100% specific for pulmonary adenocarcinoma and detected 69% of adenocarcinomas
  • Among mesotheliomas, calretinin stained 80% and N-cadherin 78%
  • Among mesotheliomas, thrombomodulin stained 53% and cytokeratin 5/6 63%
  • Among adenocarcinomas, 2 cases (6%) stained for calretinin
  • Among adenocarcinomas, 9 cases (26%) stained for N-cadherin
  • Among adenocarcinomas, 2 of 35 (6%) stained for thrombomodulin
  • Among adenocarcinomas, 2 cases (6%) stained for cytokeratin 5/6
  • Tumours negative for both E-cadherin and TTF-1 were not adenocarcinomas; this group made up 78% of mesotheliomas
  • Tumours positive for E-cadherin but negative for TTF-1 needed other antibodies to be classified
  • In that remaining group, CEA stained 9 of 11 adenocarcinomas and none of the 9 E-cadherin positive mesotheliomas
  • In that remaining group, calretinin stained all 9 E-cadherin positive mesotheliomas
  • Cytokeratin 5/6 stained 92% of epithelioid mesotheliomas but only 14% of sarcomatoid mesotheliomas
• The authors' conclusion: The authors concluded that E-cadherin and TTF-1 should be the first-line antibodies. Tumours that are E-cadherin positive but TTF-1 negative need a secondary panel of further antibodies.
• Limitations the authors state:
  • The antibodies chosen were not a comprehensive set
  • Thrombomodulin staining was patchy, so some mesotheliomas counted as negative may have been false negatives
  • Staining multiple tissue blocks might improve thrombomodulin sensitivity, but this is not possible with small biopsies
  • Calretinin also stained macrophages associated with the tumour, so care is needed when reading it
  • HBME-1 staining patterns were hard to interpret in individual cases

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: Immunohistochemistry, Malignant Mesothelioma, Adenocarcinoma, Lung Adenocarcinoma, Calretinin, Thyroid Transcription Factor-1 (TTF-1), Cytokeratin 5/6, Mesothelioma.

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