Validation of a minimal panel of antibodies for the diagnosis of malignant pleural mesothelioma

Our plain-English summary of Validation of a minimal panel of antibodies for the diagnosis of malignant pleural mesothelioma, by S.C. Kao, K. Griggs, K. Lee, et al (Pathology, 2011).

The study

• Authors: S.C. Kao, K. Griggs, K. Lee, N. Armstrong, S. Clarke, J. Vardy, N. van Zandwijk, J. Burn, B.C. McCaughan, D.W. Henderson, S. Klebe
• Journal: Pathology
• Published: 2011;43(4):313-7
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aims: We previously established the use of a minimal panel of antibodies as sufficient to diagnose most epithelial malignant mesothelioma (MPM). We aimed to validate this approach and investigate the utility of a D2-40 antibody.

Methods: A series of 80 MPM patients selected for surgery and 21 consecutive patients with pleural metastatic carcinoma were included. A minimal panel of antibodies, consisting of calretinin, BG8 and CD15, and D2-40 was investigated.

Results: There were 61 epithelial and 19 biphasic MPM as well as 12 metastatic lung, six breast (5 ductal adenocarcinomas, 1 mixed ductal/lobular adenocarcinoma), two serous papillary ovarian carcinomas and one moderately differentiated colorectal adenocarcinoma. The sensitivity of positive calretinin labelling to confirm the diagnosis of MPM was 97.5%, while the 'diagnostic sensitivities' of lack of labelling for BG8 and CD15 were 91.3% and 97.5%, respectively. The use of calretinin, BG8 and CD15 resulted in correct classification in 97.5% of all MPMs. All MPM cases investigated showed at least focal positive D2-40 labelling.

Conclusions: We have validated the usefulness of a minimal panel of antibodies with calretinin, BG8 and CD15 as the initial step to the diagnosis of MPM. D2-40 emerged as a helpful diagnostic tool for cases where our initial approach failed to conclusively diagnose MPM.

In plain English

This Australian study tested whether a small set of laboratory stains (antibodies) could tell malignant pleural mesothelioma apart from other cancers that had spread to the pleura, the lining around the lung. The authors had proposed a three-antibody panel (calretinin, BG8 and CD15) in an earlier study. Here they checked it on a new group: tissue from 80 mesothelioma patients selected for surgery (61 epithelial and 19 biphasic), and from 21 patients whose lung, breast, ovarian or colorectal cancer had spread to the pleura. They also tested a fourth antibody, D2-40. Calretinin stained 97.5% of the mesotheliomas. The three-antibody panel classified 78 of the 80 mesotheliomas and all 21 spread cancers correctly. The two missed mesotheliomas lacked calretinin staining but stained for D2-40. D2-40 stained every mesothelioma and none of the spread cancers. The authors concluded the panel was useful as a first diagnostic step, with D2-40 helpful when that step was inconclusive. They named the small number of comparison cancers as a limitation. The study did not examine 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 validation study of immunohistochemistry (antibody staining) on archived tumour tissue, testing a previously published three-antibody classification model and an added marker, D2-40
• Who was studied: 80 patients with malignant pleural mesothelioma (61 epithelial, 19 biphasic, none sarcomatoid). They came from 85 patients considered eligible for extrapleural pneumonectomy in Sydney between October 1994 and October 2009. The controls were 21 patients with metastatic pleural carcinoma (12 lung, 6 breast, 2 ovarian, 1 colorectal) diagnosed at Flinders Medical Centre, Adelaide.
• Exposure: No asbestos exposure was studied. The study tested staining with four antibodies (calretinin, BG8, CD15 and D2-40) on tumour tissue.
• Main results:
  • Calretinin: sensitivity 97.5% and specificity 100% for mesothelioma, across all 101 cases
  • D2-40: 100% sensitivity and 100% specificity. All 80 mesotheliomas stained at least focally, and none of the 21 metastatic carcinomas stained.
  • Lack of staining for BG8 and for CD15 had 'diagnostic sensitivities' of 91.3% and 97.5% in the mesotheliomas
  • The specificity of lack of BG8 staining was 65%; the specificity of lack of CD15 staining was 35%
  • Positive calretinin plus negative BG8 identified 90% of the 80 mesotheliomas. Adding negative CD15 raised this to 97.5% (78 of 80).
  • All 21 metastatic carcinomas were correctly classified by the three-antibody panel
  • The two mesotheliomas without calretinin staining (1 epithelial, 1 biphasic) both stained positively for D2-40
  • In the 19 biphasic mesotheliomas, the epithelial part stained for calretinin in 19 (100%) and for D2-40 in 17 (89%). The sarcomatoid part stained for calretinin in 4 (21%) and for D2-40 in 12 (63%).
  • When these patients were first diagnosed, the median number of antibodies used was five (range 0 to 15). Three patients had no immunohistochemistry at initial diagnosis.
• The authors' conclusion: The authors concluded that they had validated the calretinin, BG8 and CD15 panel as the first step in diagnosing malignant mesothelioma. They found D2-40 a sensitive and specific marker where uncertainty remained, and said it should be evaluated prospectively in a larger cohort.
• Limitations the authors state:
  • Only a relatively small number of metastatic pleural carcinomas was included, which may explain the high specificity observed
  • The number of cases tested for D2-40 is still relatively small
  • The series contained no sarcomatoid mesotheliomas
  • The panel is intended only for the first separation of mesothelioma from carcinoma. Additional antibodies may be needed, for example to find where a carcinoma started.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Malignant Mesothelioma, Podoplanin (D2-40), Carcinoma, Calretinin, Biphasic Mesothelioma, Adenocarcinoma.

Related studies

• Differential Diagnosis of Epithelioid Malignant Mesothelioma With Lung and Breast Pleural Metastasis: A Systematic Review Compared With a Standardized Panel of Antibodies-A New Proposal That May Influence Pathologic Practice — N. Le Stang, L. Burke, et al. (2020)
• Validation of tissue microarray technology in malignant pleural mesothelioma — S.C. Kao, K. Lee, et al. (2011)
• Challenges and controversies in the diagnosis of mesothelioma: Part 1. Cytology-only diagnosis, biopsies, immunohistochemistry, discrimination between mesothelioma and reactive mesothelial hyperplasia, and biomarkers — D.W. Henderson, G. Reid, et al. (2013)
• Immunohistochemical analysis still has a limited role in the diagnosis of malignant mesothelioma. A study of thirteen antibodies — F. Roberts, C.M. Harper, et al. (2001)
• Accuracy of diagnostic biopsy for the histological subtype of malignant pleural mesothelioma — S.C. Kao, T.D. Yan, et al. (2011)
• An immunohistochemical comparison of two TTF-1 monoclonal antibodies in atypical squamous lesions and sarcomatoid carcinoma of the lung, and pleural malignant mesothelioma — S. Klebe, A. Swalling, et al. (2016)

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