Immunohistochemistry and molecular diagnostics of pleural malignant mesothelioma

Our plain-English summary of Immunohistochemistry and molecular diagnostics of pleural malignant mesothelioma, by P.G. Betta, C. Magnani, T. Bensi, et al (Archives of Pathology & Laboratory Medicine, 2012).

The study

• Authors: P.G. Betta, C. Magnani, T. Bensi, N.F. Trincheri, S. Orecchia
• Journal: Archives of Pathology & Laboratory Medicine
• Published: 2012;136(3):253-61
• Type of article: Review
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Context: The pathologic approach to pleural-based lesions is stepwise and uses morphologic assessment, correlated with clinical and imaging data supplemented by immunohistochemistry (IHC), and more recently, molecular tests, as an aid for 2 main diagnostic problems: malignant mesothelioma (MM) versus other malignant tumors and malignant versus reactive mesothelial proliferations.

Objective: To present the current knowledge regarding IHC and molecular tests with respect to MM diagnosis, and in particular, the differentiation of the epithelioid type of MM from carcinoma metastatic to the pleural cavity.

Data Sources: A review of immunohistochemical features of 286 consecutive MMs from 459 cases of pleural pathology, diagnosed during routine practice from 2003 to 2009. A survey of biomedical journal literature from MedLine/PubMed (US National Library of Medicine) focused on MM and associated tissue-based diagnostic IHC markers and molecular tests.

Conclusions: The search for a single diagnostic marker of MM has so far been discouraging, given the biologic and phenotypic tumor heterogeneity of MM. The use of antibody panels has gained unanimous acceptance especially in the differential diagnosis between MM and metastatic carcinoma, whereas the usefulness of IHC is more limited when dealing with spindle cell malignancies or distinguishing malignant from reactive mesothelium. A great degree of interlaboratory variability in antibody combinations and clone selection within diagnostic panels still exists. Current investigations aim at selecting the most suitable and cost-effective combination of antibodies by using novel statistical approaches for assessing diagnostic performance beyond the traditional measures of sensitivity and specificity.

In plain English

This article reviewed how pathologists use immunohistochemistry (antibody staining of tissue) and newer molecular tests to diagnose pleural malignant mesothelioma. It combined published literature with the authors' own cases: 286 consecutive "definite" pleural mesotheliomas (211 epithelioid, 47 mixed, 28 sarcomatoid), 67 pleural metastatic carcinomas and 106 benign pleural lesions, diagnosed from 2003 to 2009 in Alessandria, Italy. The province includes Casale Monferrato, where Italy's largest asbestos-cement factory operated. In telling epithelioid or mixed mesothelioma apart from adenocarcinoma spread to the pleura, keratin 5 stained 138 of 139 tested mesotheliomas (99%), calretinin 248 of 252 (98%) and WT-1 43 of 44 (98%). Podoplanin stained none of 18 tested metastatic adenocarcinomas (100% specificity). Among 28 sarcomatoid cases, 27 (96.4%) reacted to at least one keratin antibody. The authors concluded that the search for a single diagnostic marker had been discouraging. They found antibody panels widely accepted for separating mesothelioma from metastatic carcinoma. Staining was of more limited use for spindle cell tumors and for telling malignant from reactive mesothelium. The authors said molecular methods reported by other researchers still need validation in large studies.

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: Review: a survey of published literature plus a review of staining results from the authors' own pathology case database
• Who was studied: Cases from the pathology laboratory in Alessandria, northwest Italy, 2003 to 2009: 286 consecutive definite pleural malignant mesotheliomas (211 epithelioid, 47 mixed, 28 sarcomatoid), 67 pleural metastatic carcinomas and 106 benign serosal lesions
• Exposure: Asbestos exposure was not studied. The setting is a province containing Casale Monferrato, home of an asbestos-cement factory from 1907 to 1986. The study examined diagnostic antibody staining and molecular tests.
• Main results:
  • Epithelioid or mixed mesothelioma versus pleural metastatic adenocarcinoma, authors' series: keratin 5 had the highest sensitivity (99%, 138 of 139 tested mesotheliomas). Calretinin followed (98%, 248 of 252), then WT-1 (98%, 43 of 44).
  • Same comparison: podoplanin had the highest specificity (100%). It stained 0 of 18 tested pleural metastatic adenocarcinomas and 27 of 30 tested mesotheliomas.
  • In the authors' data, a published 3-antibody panel (calretinin and MOC31, with Ber-EP4 in place of BG8) showed 98% sensitivity and 90% specificity
  • A TTF-1 plus WT-1 panel showed 96% sensitivity and 88% specificity in the authors' data, which for these antibodies covered only 41 subjects
  • A 2-antibody panel (calretinin, with Ber-EP4 in place of BG8) showed 93% sensitivity and 97% specificity in the authors' data
  • Sarcomatoid mesotheliomas: 27 of 28 cases (96.4%) reacted to at least one keratin antibody, and 19 of 28 (67.9%) were calretinin positive
• The authors' conclusion: The authors concluded that the search for a single diagnostic marker of mesothelioma had been discouraging because of tumor heterogeneity. Antibody panels were widely accepted for separating mesothelioma from metastatic carcinoma. Immunohistochemistry was more limited for spindle cell tumors and for distinguishing malignant from reactive mesothelium. Novel molecular approaches need validation in large prospective studies.
• Limitations the authors state:
  • Not all cases could be stained, because many referral cases lacked paraffin blocks or unstained slides
  • The data for the TTF-1 plus WT-1 panel were limited to 41 subjects
  • The authors' experience with WT-1 and podoplanin in sarcomatoid mesothelioma was too limited to draw conclusions

Topics

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

Medical terms in this study, explained in our Lexicon: Immunohistochemistry, Malignant Mesothelioma, Epithelioid, Carcinoma, Pleural Cavity, Pathology, Differential Diagnosis, Spindle Cell.

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