Utility of a CEA, CD15, calretinin, and CK5/6 panel for distinguishing between mesotheliomas and pulmonary adenocarcinomas in clinical practice

Our plain-English summary of Utility of a CEA, CD15, calretinin, and CK5/6 panel for distinguishing between mesotheliomas and pulmonary adenocarcinomas in clinical practice, by T. Mohammad, J. Garratt, E. Torlakovic, et al (The American Journal of Surgical Pathology, 2012).

The study

• Authors: T. Mohammad, J. Garratt, E. Torlakovic, B. Gilks, A. Churg
• Journal: The American Journal of Surgical Pathology
• Published: 2012;36(10):1503-8
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Most reports on antibodies that claimed to separate mesothelioma from pulmonary adenocarcinoma originated from academic centers or specialized immunohistochemistry laboratories, but little is known about how such stains perform in general practice laboratories. The Canadian Immunohistochemistry Quality Control program circulates tissue array slides to laboratories across Canada; these are stained and then interpreted by the local laboratory and by a set of experienced reviewers. For Canadian Immunohistochemistry Quality Control run 16, tissue array slides from 16 pulmonary adenocarcinomas and 6 mesotheliomas were stained in 36 different laboratories for CEA, CD15, CK5/6, and calretinin. A total of 736 results (cores) were interpretable. If 3 of 4 staining results concordant with the diagnosis was accepted as definitive, 166/192 (86.4%) mesothelioma cores and 461/544 (84.7%) adenocarcinoma cores were correctly diagnosed. However, if 4 of 4 concordant markers were required, then 93/192 (48.4%) mesothelioma cores and 265/544 (48.7%) adenocarcinoma cores were correctly diagnosed. Only 3/192 (1.6%) mesothelioma cores were incorrectly classified as carcinomas and 8/544 (1.5%) of adenocarcinoma cores incorrectly classified as mesotheliomas on the basis of the immunoprofile (ie, 3 of 4 or 4 of 4 marker results were discordant with the diagnosis). We conclude that, in a study based on results from nonspecialized laboratories, the combination of CEA, CD15, calretinin, and CK5/6, used as a panel, has a very low false-positive rate when separating pulmonary adenocarcinomas from mesotheliomas; however, single negative or incorrect results are common, therefore the panel is only useful diagnostically if 3 of 4 correct results are deemed acceptable for diagnosis.

In plain English

This study tested how well four laboratory stains work in ordinary, non-specialized pathology laboratories for telling malignant mesothelioma apart from lung adenocarcinoma, a type of lung cancer. Through the Canadian Immunohistochemistry Quality Control program, slides holding small tissue samples from 6 epithelial or mixed mesotheliomas and 16 primary lung adenocarcinomas were stained in 36 Canadian laboratories. Two stains, calretinin and CK5/6, are expected to mark mesothelioma. The other two, CEA and CD15, are expected to mark adenocarcinoma. Of 736 usable samples, 192 were mesothelioma and 544 adenocarcinoma. When 3 of 4 matching stains were accepted, 166 of 192 (86.4%) mesothelioma samples and 461 of 544 (84.7%) adenocarcinoma samples were correctly identified. When all 4 stains had to match, this fell to 93 of 192 (48.4%) and 265 of 544 (48.7%). Only 3 mesothelioma samples (1.6%) were wrongly classed as adenocarcinoma, and 8 adenocarcinoma samples (1.5%) as mesothelioma. The authors concluded that the panel had a very low false-positive rate but is useful only if 3 of 4 correct results are accepted. 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: Multi-laboratory diagnostic performance study run through a national immunohistochemistry quality control program (CIQC run 16), using tissue microarray slides
• Who was studied: Tissue samples from 6 epithelial or mixed epithelial and sarcomatoid mesotheliomas and 16 primary lung adenocarcinomas from the files of Vancouver General Hospital. Five sarcomatoid mesotheliomas were excluded. The slides were stained by 36 of 68 participating Canadian laboratories (those that performed all 4 stains), giving 736 analyzable cores: 192 mesothelioma and 544 adenocarcinoma.
• Exposure: No asbestos exposure was studied. The study evaluated a four-stain immunohistochemistry panel: calretinin and CK5/6 as mesothelioma markers, and CD15 and monoclonal CEA as adenocarcinoma markers, each applied with the laboratory's own protocols and antibodies.
• Main results:
  • Accepting 3 or 4 correct stains: 166 of 192 mesothelioma cores (86.4%) and 461 of 544 adenocarcinoma cores (84.7%) were correctly identified
  • Requiring all 4 correct stains: 93 of 192 mesothelioma cores (48.4%) showed the perfect pattern
  • Requiring all 4 correct stains: 265 of 544 adenocarcinoma cores (48.7%) were correctly identified
  • 3 mesothelioma cores (1.6%) were incorrectly identified as adenocarcinomas
  • 8 adenocarcinoma cores (1.5%) were incorrectly identified as mesotheliomas
  • 23 of 192 mesothelioma cores (12%) gave indeterminate results
  • 75 of 544 adenocarcinoma cores (13.8%) gave indeterminate results
  • Specificity of the panel was 98.5% for mesotheliomas and 98.4% for adenocarcinomas
  • For mesotheliomas, sensitivity was 90.2% when 3 correct stains were accepted as diagnostic
  • Taken individually, CK5/6 had lower sensitivity and somewhat lower specificity than the other three markers (Table 3: sensitivity 54.3%, specificity 89.0%)
• The authors' conclusion: The authors concluded that the panel gave overall good separation of pulmonary adenocarcinomas from mesotheliomas, with a very low false-positive rate in routine clinical practice, but that 3 of 4 'correct' markers must be accepted as diagnostic for the panel to be useful
• Limitations the authors state:
  • Some aberrant results may reflect the limited sampling in tissue microarrays or tissue heterogeneity, and might not be seen in regular tissue sections
  • Only a little more than half of participating laboratories could perform all 4 stains
  • Specialists might argue that better antibody combinations exist, though the authors state there is no consensus on what they are

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: Calretinin, Mesothelioma, Adenocarcinoma, Immunohistochemistry, Carcinoma.

Related studies

• The diagnostic utility of D2-40, calretinin, CK5/6, desmin and MOC-31 in the differentiation of mesothelioma from adenocarcinoma in pleural effusion cytology — T.S. Hyun, M. Barnes, et al. (2012)
• 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)
• Immunohistochemical panels for differentiating epithelial malignant mesothelioma from lung adenocarcinoma: a study with logistic regression analysis — R. Carella, G. Deleonardi, et al. (2001)
• 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)
• 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)
• Expression of thrombomodulin, calretinin, cytokeratin 5/6, D2-40 and WT-1 in a series of primary carcinomas of the lung: an immunohistochemical study in comparison with epithelioid pleural mesothelioma — C.E. Comin, L. Novelli, et al. (2014)

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