Role of immunohistochemistry in differentiating epithelial mesothelioma from adenocarcinoma. Review and update

Our plain-English summary of Role of immunohistochemistry in differentiating epithelial mesothelioma from adenocarcinoma. Review and update, by N.G. Ordóñez (American Journal of Clinical Pathology, 1999).

The study

• Author: N.G. Ordóñez
• Journal: American Journal of Clinical Pathology
• Published: 1999;112(1):75-89
• Type of article: Review
• Cited by: 47 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

This review examined the immunohistochemical markers most commonly used to tell malignant epithelial mesothelioma apart from adenocarcinoma that has spread to the serosal membranes. The author described this distinction as difficult with histochemical stains and electron microscopy alone. Because no specific marker for mesothelioma had been recognized, diagnosis depended on panels of antibodies. The author summarized published studies and his own experience at the University of Texas M. D. Anderson Cancer Center. He emphasized newer markers that can be used on formalin-fixed, routinely processed tissue. In his studies, cytokeratin 5/6 was found in 40 of 40 mesotheliomas but in none of 30 pulmonary adenocarcinomas. Calretinin was strongly expressed in 38 of 38 epithelial mesotheliomas, while 14 (9%) of 155 adenocarcinomas showed focal staining. Vimentin, desmin, polymorphic epithelial mucins, 44-3A6, S-100 protein, HBME-1 and OV632 were judged to have little or no practical value. The author concluded that calretinin and cytokeratin 5/6 appeared to be the most useful positive markers for mesothelioma. MOC-31, CEA, B72.3 and the BG-8 anti-Lewis(y) antibody were the best negative markers. Leu-M1, Ber-EP4 and thrombomodulin could be used as secondary markers when other results were equivocal. N-cadherin and E-cadherin needed further study.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This article was a review by a single author at the University of Texas M. D. Anderson Cancer Center. It covered immunohistochemical stains that pathologists use to tell malignant epithelial mesothelioma apart from adenocarcinoma that has spread to the serosal membranes (the linings of body cavities). It summarized published studies and the author's own earlier work, with emphasis on markers that work on routinely processed tissue. It did not study asbestos or any other exposure. The author noted that no specific marker for mesothelioma had been recognized, so diagnosis depends on panels of stains. In a recent study by the author, calretinin stained 38 of 38 epithelial mesotheliomas but only 14 (9%) of 155 adenocarcinomas, and in those only focally. The author judged vimentin and HBME-1 to have little or no practical value. The author concluded that calretinin and cytokeratin 5/6 appeared to be the most useful markers found in mesotheliomas. MOC-31, CEA, B72.3 and the BG-8 antibody were the best of the markers found in adenocarcinomas. Leu-M1, Ber-EP4 and thrombomodulin could serve as secondary markers, and N-cadherin and E-cadherin needed more study.

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: Narrative review of published studies on immunohistochemical markers, including the author's own published and unpublished experience
• Who was studied: Published studies of malignant epithelial mesotheliomas and adenocarcinomas metastatic to the serosal membranes, with emphasis on markers usable on formalin-fixed, routinely processed tissue; author based at University of Texas M. D. Anderson Cancer Center, Houston
• Exposure: Not addressed: the review concerns diagnostic laboratory stains; asbestos and fiber exposure are not discussed
• Main results:
  • In a recent investigation by the author, calretinin showed strong reactivity in 38 of 38 epithelial mesotheliomas, while 14 (9%) of 155 adenocarcinomas of various origin showed focal staining
  • In the author's earlier study, cytokeratin 5/6 reactivity was shown in 40 of 40 mesotheliomas
  • In the same cytokeratin 5/6 study, focal weak reactivity occurred in 14 of 93 nonpulmonary adenocarcinomas
  • In the author's published study, Ber-EP4 stained 18 (26%) of 70 mesotheliomas and 101 (92%) of 110 adenocarcinomas
  • In the author's experience, B72.3 reactivity occurs in about 2% to 5% of epithelial mesotheliomas and 80% of lung adenocarcinomas
  • In the author's experience, thrombomodulin reactivity is detected in approximately 75% to 80% of epithelial mesotheliomas and about 10% to 15% of adenocarcinomas
  • In a cited recent study, only 7 (16%) of 45 papillary serous carcinomas reacted for CEA, limiting CEA's value for that comparison
  • The author judged vimentin immunostaining to have no practical utility in diagnosing mesothelioma
  • The author judged HBME-1 to have little or no practical value in differentiating mesotheliomas from adenocarcinomas
• The authors' conclusion: The author concluded that calretinin and cytokeratin 5/6 appear to be the most useful positive markers for mesothelioma. MOC-31, CEA, B72.3 and the BG-8 anti-Lewis y antibody were judged the best negative markers. Leu-M1, Ber-EP4 and thrombomodulin can be secondary markers when other results are equivocal. N-cadherin and E-cadherin appear promising but need more study.
• Limitations the authors state:
  • No specific marker for mesothelioma has been recognized, so diagnosis depends on panels of antibodies that differ in specificity and sensitivity
  • Only polyclonal calretinin antibodies were commercially available, so sensitivity and specificity can differ between lots
  • Evidence on N-cadherin and E-cadherin was insufficient to establish their practical utility

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, Mesothelioma, Adenocarcinoma, Cytokeratin 5/6, Calretinin, Desmin, S-100, HBME-1.

Related studies

• Value of the MOC-31 monoclonal antibody in differentiating epithelial pleural mesothelioma from lung adenocarcinoma — N.G. Ordóñez (1998)
• Value of the Ber-EP4 antibody in differentiating epithelial pleural mesothelioma from adenocarcinoma. The M.D. Anderson experience and a critical review of the literature — N.G. Ordóñez (1998)
• Immunohistochemical panels for differentiating epithelial malignant mesothelioma from lung adenocarcinoma: a study with logistic regression analysis — R. Carella, G. Deleonardi, et al. (2001)
• Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies — A.S. Abutaily, B.J. Addis, et al. (2002)
• Calretinin, thrombomodulin, CEA, and CD15: a useful combination of immunohistochemical markers for differentiating pleural epithelial mesothelioma from peripheral pulmonary adenocarcinoma — C.E. Comin, L. Novelli, et al. (2001)
• Cytological differential diagnosis among adenocarcinoma, epithelial mesothelioma, and reactive mesothelial cells in serous effusions by immunocytochemistry — X.Y. Su, G.D. Li, et al. (2011)

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