MUC4 immunohistochemistry is useful in distinguishing epithelioid mesothelioma from adenocarcinoma and squamous cell carcinoma of the lung

Our plain-English summary of MUC4 immunohistochemistry is useful in distinguishing epithelioid mesothelioma from adenocarcinoma and squamous cell carcinoma of the lung, by A.S. Mawas, V.J. Amatya, K. Kushitani, et al (Scientific Reports, 2018).

The study

• Authors: A.S. Mawas, V.J. Amatya, K. Kushitani, Y. Kai, Y. Miyata, M. Okada, Y. Takeshima
• Journal: Scientific Reports
• Published: 2018;8(1):134
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The differential diagnosis of epithelioid mesothelioma from lung adenocarcinoma and squamous cell carcinoma requires the positive and negative immunohistochemical markers of mesothelioma. The IMIG guideline has suggested the use of Calretinin, D2-40, WT1, and CK5/6 as mesothelial markers, TTF-1, Napsin-A, Claudin 4, CEA as lung adenocarcinoma markers p40, p63, CK5/6, MOC-31 as squamous cell markers. However, use of other immunohistochemical markers is still necessary. We evaluated 65 epithelioid mesotheliomas, 60 adenocarcinomas, and 57 squamous cell carcinomas of the lung for MUC4 expression by immunohistochemistry and compared with the previously known immunohistochemical markers. MUC4 expression was not found in any of 65 cases of epithelioid mesothelioma. In contrast, MUC4 expression was observed in 50/60(83.3%) cases of lung adenocarcinoma and 50/56(89.3%) cases of lung squamous cell carcinoma. The negative MUC4 expression showed 100% sensitivity, 86.2% specificity and accuracy rate of 91.2% to differentiate epithelioid mesothelioma from lung carcinoma. The sensitivity, specificity, and accuracy of MUC4 are comparable to that of previously known markers of lung adenocarcinoma and squamous cell carcinoma, namely CEA, Claudin 4 and better than that of MOC-31. In conclusion, MUC4 immunohistochemistry is useful for differentiation of epithelioid mesothelioma from lung carcinoma, either adenocarcinoma or squamous cell carcinoma.

In plain English

This laboratory study from Hiroshima University, Japan, tested whether staining tumor tissue for a protein called MUC4 could help pathologists tell epithelioid mesothelioma apart from two lung cancers, adenocarcinoma and squamous cell carcinoma. The authors stained stored samples from 65 epithelioid mesotheliomas, 60 lung adenocarcinomas and 57 squamous cell carcinomas (56 appear in the results tables), and compared MUC4 with established markers. The article did not study asbestos exposure. MUC4 was absent in all 65 mesotheliomas but present in 50 of 60 adenocarcinomas (83.3%) and 50 of 56 squamous cell carcinomas (89.3%). Using a negative MUC4 result to pick out mesothelioma from all the lung cancers gave 100% sensitivity, 86.2% specificity and 91.2% accuracy. Two other markers, CEA and Claudin 4, performed better, while MUC4 did better than a marker called MOC-31. A few adenocarcinomas that were negative for CEA or Claudin 4 were MUC4-positive. The authors concluded that MUC4 can be added as an extra marker for this distinction. They noted that the number of cases was limited and called for a larger follow-up 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: Diagnostic laboratory study: immunohistochemical staining of archived tumor tissue samples, comparing MUC4 with other established markers
• Who was studied: Archived tumor specimens from 65 epithelioid mesotheliomas, 60 lung adenocarcinomas and 57 lung squamous cell carcinomas, held by the Department of Pathology, Hiroshima University, Japan. The results tables report 56 squamous cell carcinomas. Mean patient age was 69 in each group. The mesothelioma patients were 61 men and 4 women. Collection dates were not given.
• Exposure: No asbestos or other exposure was studied. The factor examined was a diagnostic test: MUC4 immunohistochemistry (antibody clone 8G7), compared with markers including calretinin, D2-40, WT1, CK5/6, CEA, Claudin 4, MOC-31, TTF-1, Napsin-A, p63 and p40.
• Main results:
  • MUC4 was not present in any of the 65 epithelioid mesotheliomas (0%).
  • MUC4 was present in 50 of 60 lung adenocarcinomas (83.3%) and in 50 of 56 lung squamous cell carcinomas (89.3%).
  • Used as a negative marker to distinguish epithelioid mesothelioma from all lung cancers combined, MUC4 had 100% sensitivity, 86.2% specificity and 91.2% accuracy.
  • Against lung adenocarcinoma alone, MUC4 had 100% sensitivity, 83.3% specificity and 92% accuracy.
  • Against lung squamous cell carcinoma alone, MUC4 had 100% sensitivity, 89.3% specificity and 95% accuracy.
  • Against all lung cancers combined, CEA was the best marker (sensitivity 100%, specificity 98.3%, accuracy 98.9%), followed by Claudin 4 (100%, 96.6%, 97.8%). MUC4's accuracy was better than that of MOC-31.
  • Some adenocarcinomas negative for CEA and/or Claudin 4 showed MUC4 expression, including one case negative for both.
  • MUC4 was not found in the normal mesothelial layer of the visceral pleura present in 39 of the lung cancer samples.
• The authors' conclusion: The authors concluded that MUC4 can be added as an additional positive marker of non-small cell lung carcinoma and a negative marker to distinguish epithelioid mesothelioma from lung adenocarcinoma and squamous cell carcinoma.
• Limitations the authors state:
  • The authors stated that the study included a limited number of cases and needs a follow-up study with larger numbers.

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: Immunohistochemistry, Epithelioid, Mesothelioma, Adenocarcinoma, Squamous Cell Carcinoma, Differential Diagnosis, Lung Adenocarcinoma, IMIG.

Related studies

• Utility and pitfalls of immunohistochemistry in the differential diagnosis between epithelioid mesothelioma and poorly differentiated lung squamous cell carcinoma — K. Kushitani, V.J. Amatya, et al. (2017)
• MUC4, a novel immunohistochemical marker identified by gene expression profiling, differentiates pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma — V.J. Amatya, K. Kushitani, et al. (2017)
• Small orangiophilic squamous-like cells: an underrecognized and useful morphological feature for the diagnosis of malignant mesothelioma in pleural effusion cytology — L. Chen, S.G. Caldero, et al. (2014)
• Claudin-4 immunohistochemistry is highly effective in distinguishing adenocarcinoma from malignant mesothelioma in effusion cytology — V.Y. Jo, E.S. Cibas, et al. (2014)
• 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)
• 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)

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