Immunohistochemical panels for differentiating epithelial malignant mesothelioma from lung adenocarcinoma: a study with logistic regression analysis

Our plain-English summary of Immunohistochemical panels for differentiating epithelial malignant mesothelioma from lung adenocarcinoma: a study with logistic regression analysis, by R. Carella, G. Deleonardi, A. D'Errico, et al (The American Journal of Surgical Pathology, 2001).

The study

• Authors: R. Carella, G. Deleonardi, A. D'Errico, A. Salerno, E. Egarter-Vigl, C. Seebacher, G. Donazzan, W.F. Grigioni
• Journal: The American Journal of Surgical Pathology
• Published: 2001;25(1):43-50
• Cited by: 92 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Immunohistochemistry provides an important indicator for differential diagnosis between pleural malignant mesothelioma and lung adenocarcinoma, which have complex therapeutic and medicolegal implications. To pinpoint a reliable, restricted panel of markers, the authors evaluated the efficacy of select commercial antibodies in a series of patients with confirmed clinicopathologic diagnosis of mesothelioma or lung adenocarcinoma with the aid of multiple logistic classification tables. Specimens of 46 mesotheliomas and 20 lung adenocarcinomas were examined with calretinin, thrombomodulin, cytokeratins (CKs) 5/6, and high-molecular weight CKs (indicators of mesothelioma), alongside MOC 31, Ber-EP4, and carcinoembryonic antigen (CEA; indicators of lung adenocarcinoma). Of the mesotheliomas, 40 of 46 (87%) were positive with calretinin, 29 of 46 (63%) with thrombomodulin, 40 of 46 (87%) with CKs 5/6, and 41 of 46 (89%) with high-weight CKs; five of 46 mesotheliomas (11%) were focally reactive with MOC 31, four of 46 (9%) with Ber-EP4, and two of 46 (4%) with CEA. Of the lung adenocarcinomas, 18 of 20 (90%) were positive with MOC 31, 20 of 20 (100%) with Ber-EP4, and 17 of 20 (85%) with CEA; and two of 20 (10%) were focally reactive with calretinin, one of 20 (5%) with thrombomodulin, none of 20 (0%) with CKs 5/6, and five of 20 (25%) with high-weight CKs. Multiple logistic modeling indicated two batteries of three antibodies permitting more than 98% overall accuracy: Ber-EP4 plus CKs 5/6 plus calretinin, and Ber-EP4 plus CKs 5/6 plus CEA.

In plain English

This laboratory study came from two hospitals in Bologna and Bolzano, Italy. It tested how well seven commercially available antibody stains (immunohistochemistry) tell pleural malignant mesothelioma apart from lung adenocarcinoma, a type of lung cancer. The authors used archived tissue from 46 patients with mesothelioma and 20 patients with lung adenocarcinoma. The article did not report on asbestos exposure. Calretinin stained 40 of 46 mesotheliomas and 2 of 20 adenocarcinomas. Cytokeratins 5/6 stained 40 of 46 mesotheliomas and the adenocarcinoma tissue of none of the 20 lung cancers. Ber-EP4 stained all 20 adenocarcinomas and 4 of 46 mesotheliomas. CEA stained 17 of 20 adenocarcinomas and 2 of 46 mesotheliomas. In statistical modelling, two three-stain combinations each classified more than 98% of cases correctly, matching the four-stain model. Both combined Ber-EP4 and cytokeratins 5/6 with either calretinin or CEA. The authors concluded that a limited battery of markers can help distinguish epithelial mesothelioma from lung adenocarcinoma, and that the two three-stain panels were equally reliable.

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 diagnostic study of archived tissue specimens, testing seven antibody stains individually and in combination with logistic regression analysis
• Who was studied: Archived tissue from 46 patients with malignant mesothelioma (14 women, 32 men), who had pleural biopsy or surgical decortication between 1976 and 1998 at hospitals in Bologna (11) and Bolzano (35), Italy. Of these, 32 were epithelial, 10 biphasic and 4 desmoplastic. Also surgical specimens from 20 patients with primary lung adenocarcinoma (5 women, 15 men) diagnosed between 1996 and 1998 in Bologna.
• Main results:
  • Calretinin stained 40 of 46 mesotheliomas (87%) and 2 of 20 lung adenocarcinomas (10%)
  • Thrombomodulin showed diffuse staining in 29 of 46 mesotheliomas (63%) and in 1 of 20 lung adenocarcinomas (5%)
  • Cytokeratins 5/6 stained 40 of 46 mesotheliomas (87%). The adenocarcinoma tissue of all 20 lung adenocarcinomas was negative. One adenosquamous lung cancer stained only in its squamous part.
  • High-molecular weight cytokeratins stained 41 of 46 mesotheliomas (89%) and 5 of 20 lung adenocarcinomas (25%)
  • MOC 31 stained 18 of 20 lung adenocarcinomas (90%) and was focally reactive in 5 of 46 mesotheliomas (11%)
  • Ber-EP4 stained all 20 lung adenocarcinomas (100%) and showed positivity in 4 of 46 mesotheliomas (9%)
  • CEA stained 17 of 20 lung adenocarcinomas (85%) and showed focal staining in 2 of 46 mesotheliomas (4%)
  • The best two-stain combinations, calretinin plus Ber-EP4 and cytokeratins 5/6 plus Ber-EP4, each correctly identified 97% of cases
  • The three-stain combinations calretinin plus cytokeratins 5/6 plus Ber-EP4, and cytokeratins 5/6 plus Ber-EP4 plus CEA, each correctly identified more than 98% of cases. This matched the four-stain model.
• The authors' conclusion: The authors concluded that a limited battery of markers can assist in distinguishing epithelial mesothelioma from lung adenocarcinoma. They found the two three-stain panels equally reliable, so the choice between them could depend on convenience and availability.

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: Malignant Mesothelioma, Lung Adenocarcinoma, Immunohistochemistry, Differential Diagnosis, Mesothelioma, Calretinin, Ber-EP4, Carcinoembryonic Antigen (CEA).

Related studies

• 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)
• Value of mesothelial and epithelial antibodies in distinguishing diffuse peritoneal mesothelioma in females from serous papillary carcinoma of the ovary and peritoneum — R.L. Attanoos, R. Webb, et al. (2002)
• 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)
• Immunohistochemical reactivity in mesothelioma and adenocarcinoma: a stepwise logistic regression analysis — A. Dejmek, A. Hjerpe (1994)
• Utility of a CEA, CD15, calretinin, and CK5/6 panel for distinguishing between mesotheliomas and pulmonary adenocarcinomas in clinical practice — T. Mohammad, J. Garratt, et al. (2012)
• Value of the mesothelium-associated antibodies thrombomodulin, cytokeratin 5/6, calretinin, and CD44H in distinguishing epithelioid pleural mesothelioma from adenocarcinoma metastatic to the pleura — P.M. Cury, D.N. Butcher, et al. (2000)

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