Immunohistochemical analysis still has a limited role in the diagnosis of malignant mesothelioma. A study of thirteen antibodies

Our plain-English summary of Immunohistochemical analysis still has a limited role in the diagnosis of malignant mesothelioma. A study of thirteen antibodies, by F. Roberts, C.M. Harper, I. Downie, et al (American Journal of Clinical Pathology, 2001).

The study

• Authors: F. Roberts, C.M. Harper, I. Downie, R.A. Burnett
• Journal: American Journal of Clinical Pathology
• Published: 2001;116(2):253-62
• Cited by: 86 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

To identify the most accurate and useful panel to diagnose mesothelioma, we immunostained sections from 112 mesotheliomas, 18 adenocarcinomas, and 11 reactive pleural specimens with 13 antibodies. Positive results for mesotheliomas, adenocarcinomas, and reactive pleura, respectively, were CAM5.2, 111, 18, and 11; vimentin, 30, 3, and 3; HBME-1, 75, 10, and 8; thrombomodulin, 31, 2, and 2; calretinin, 43, 6, and 11; and CD44H, 68, 10, and 4. Positive results for adenocarcinoma markers in mesotheliomas and adenocarcinomas, respectively, were carcinoembryonic antigen, 1 and 15; LeuM1, 7 and 9; and Ber-EP4, 5 and 12. All reactive pleura were negative. Positive results for markers to help distinguish mesothelioma from reactive pleura in mesotheliomas, adenocarcinomas, and reactive pleura, respectively, were epithelial membrane antigen, 76, 17, and 6; p53, 78, 16, and 9; P-170 glycoprotein, 37, 4, and 2; and platelet-derived growth factor receptor beta, 31, 1, and 2. The differential diagnosis of mesothelioma from adenocarcinoma is based on negative markers. Individual mesothelial markers are of low sensitivity and specificity for mesothelioma. However, diagnostic accuracy is improved by the use of antibody panels. To date there are no antibodies that help distinguish mesothelioma from reactive pleura.

In plain English

This laboratory study from Glasgow, Scotland, tested how well 13 commercially available antibody stains help pathologists diagnose malignant mesothelioma in biopsy tissue. The authors stained archived samples from 112 mesotheliomas (100 pleural, 7 peritoneal, 1 of the tunica vaginalis testis, 2 chest wall nodules from direct spread and 2 metastases), 18 adenocarcinomas that had spread to the pleura, and 11 non-cancerous (reactive) pleural samples. Stains meant to mark mesothelioma were often positive in adenocarcinoma too. HBME-1, for example, stained 75 of 111 mesotheliomas and 10 of 18 adenocarcinomas. Stains for adenocarcinoma did better. CEA was positive in 15 of 18 adenocarcinomas but in only 1 of 112 mesotheliomas, and no mesothelioma was positive for more than one of the three adenocarcinoma stains. None of the four stains tried for separating mesothelioma from reactive pleura did so reliably. p53, for instance, stained 78 of 112 mesotheliomas and 9 of 11 reactive samples. The authors concluded that single antibodies are unreliable, that panels of antibodies improve accuracy, and that no marker reliably separated mesothelioma from reactive pleura. 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: Retrospective laboratory (diagnostic immunohistochemistry) study of archived biopsy specimens stained with 13 antibodies
• Who was studied: 112 mesotheliomas from the pathology records of the Western Infirmary (January 1994 to December 1998) and Southern General Hospital (January 1980 to December 1997), Glasgow. By site: 100 pleural, 7 peritoneal, 1 tunica vaginalis testis, 2 chest wall nodules from direct spread, 2 metastases. By subtype: 82 epithelioid, 11 sarcomatoid, 12 biphasic, 7 desmoplastic. The study also included 18 adenocarcinomas (pleural metastases, most commonly from lung) and 11 reactive pleural mesothelial proliferations, both from the Western Infirmary (January 1994 to December 1995).
• Exposure: Asbestos exposure was not studied. The study tested 13 commercially available antibodies on tissue sections: CAM5.2, vimentin, HBME-1, thrombomodulin, calretinin, CD44H, CEA, LeuM1, Ber-EP4, EMA, p53, P-170 glycoprotein and PDGFR-beta.
• Main results:
  • CAM5.2 stained all but 1 mesothelioma (111 of 112; the negative case was sarcomatoid), all adenocarcinomas and all reactive proliferations.
  • Vimentin was positive in 30 (27.7%) of 108 mesotheliomas, 3 of 18 adenocarcinomas and 3 of 11 reactive proliferations.
  • HBME-1 was positive in 75 (67.6%) of 111 mesotheliomas and in 10 (56%) of 18 adenocarcinomas.
  • Thrombomodulin was positive in 31 (27.7%) of 112 mesotheliomas and in 2 (11%) of 18 adenocarcinomas.
  • Calretinin was positive in 43 (39.8%) of 108 mesotheliomas and in all 11 reactive proliferations. The adenocarcinoma figures conflict: the text gives 8 (47%) of 17, the tables give 6 of 17.
  • CD44H was positive in 68 (60.7%) of 112 mesotheliomas and in 10 (56%) of 18 adenocarcinomas.
  • CEA was positive in 15 (83%) of 18 adenocarcinomas and in 1 mesothelioma (biphasic).
  • LeuM1 was positive in 7 (6.3%) of the mesotheliomas and in 9 (50%) of 18 adenocarcinomas. Ber-EP4 was positive in 5 (4.5%) of the mesotheliomas and in 12 (67%) of 18 adenocarcinomas. No mesothelioma stained with more than one of the three adenocarcinoma markers.
  • EMA was positive in 76 (67.9%) of 112 mesotheliomas, in 17 (94%) of the adenocarcinomas and in 6 (55%) of the reactive proliferations.
  • p53 was positive in 69.6% of mesotheliomas (78 of 112) and in 82% (9 of 11) of reactive proliferations.
  • P-170 glycoprotein was positive in 37 (34.9%) of 106 mesotheliomas and PDGFR-beta in 31 (28.4%) of 109 mesotheliomas. Each was positive in 2 (18%) of 11 reactive proliferations.
• The authors' conclusion: The authors concluded that their results show the shortcomings of relying on individual antibodies and support using panels of antibodies. They also concluded that none of the four antibodies tested for this purpose reliably distinguished mesothelioma from reactive pleural processes.
• Limitations the authors state:
  • Both observers had considerable difficulty interpreting P-170 glycoprotein and PDGFR-beta staining, which led to many equivocal results.
  • The authors suggested that the calretinin antibody they used (Chemicon) may explain the low positivity in mesotheliomas.
  • Thrombomodulin staining can give false-negative results in small biopsy specimens.
  • Some cases did not have enough material to be tested with all 13 antibodies.
  • Newer mesothelial markers were not included in the study.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Mesothelioma, Adenocarcinoma, Pleura, CAM5.2, HBME-1, Calretinin, Carcinoembryonic Antigen (CEA).

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