Update on Immunohistochemistry for the Diagnosis of Lung Cancer

Our plain-English summary of Update on Immunohistochemistry for the Diagnosis of Lung Cancer, by K. Inamura (Cancers, 2018).

The study

• Author: K. Inamura
• Journal: Cancers
• Published: 2018;10(3)
• Type of article: Review
• Cited by: 104 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Immunohistochemistry is a widely available technique that is less challenging and can provide clinically meaningful results quickly and cost-efficiently in comparison with other techniques. In addition, immunohistochemistry allows for the evaluation of cellular localization of proteins in the context of tumor structure. In an era of precision medicine, pathologists are required to classify lung cancer into specific subtypes and assess biomarkers relevant to molecular-targeted therapies. This review summarizes the hot topics of immunohistochemistry in lung cancer, including (i) adenocarcinoma vs squamous cell carcinoma; (ii) neuroendocrine markers; (iii) ALK, ROS1, and EGFR; (iv) PD-L1 (CD274); (v) lung carcinoma vs malignant mesothelioma; and (vi) NUT carcinoma. Major pitfalls in evaluating immunohistochemical results are also described.

In plain English

This article was a narrative review by a single author at the Cancer Institute in Tokyo, published in 2018. It described how immunohistochemistry (staining tissue to detect specific proteins) is used to diagnose lung cancer. It did not report a new patient study; the marker test results it quoted came from earlier published studies. Topics included telling adenocarcinoma from squamous cell carcinoma, neuroendocrine markers, ALK, ROS1 and EGFR, PD-L1, NUT carcinoma, and telling lung carcinoma from malignant mesothelioma. The review noted that asbestos exposure is the main risk factor for malignant mesothelioma. It reported that the International Mesothelioma Interest Group recommends at least two mesothelial and two carcinoma markers, in addition to cytokeratins, for this distinction. In one cited study, DAB2 and Intelectin-1 were positive in 80% and 76% of epithelioid mesotheliomas, and in 3% and 0% of lung adenocarcinomas. Loss of BAP1 staining was described as often seen in epithelioid and biphasic mesothelioma but relatively uncommon in the sarcomatoid subtype. The author concluded that immunohistochemistry plays an essential role in diagnosing mesothelioma, together with morphological, clinical and radiological features.

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 (single author); no original patient study
• Who was studied: No study population. The review covered published literature on immunohistochemistry in lung cancer, including the distinction between lung carcinoma and malignant mesothelioma.
• Exposure: No exposure was studied. The review mentions asbestos exposure only as background, as the main risk factor for malignant mesothelioma.
• Main results:
  • The review described malignant mesothelioma subtypes as epithelioid (60–80%), sarcomatoid (under 10%) and biphasic (10–15%).
  • The review reported that the International Mesothelioma Interest Group recommends at least two mesothelial and two carcinoma markers, in addition to cytokeratins, to distinguish malignant mesothelioma from carcinoma.
  • The mesothelial markers listed were calretinin, podoplanin (clone D2-40), CK5 or CK5/6, and WT1. The markers listed as suggesting lung adenocarcinoma were TTF-1, Napsin A, CEA, claudin 4, Ber-EP4 and MOC31.
  • In a cited study (not this review's own data), DAB2 and Intelectin-1 were positive in 80% and 76% of epithelioid mesotheliomas, and in 3% and 0% of lung adenocarcinomas, respectively.
  • Citing earlier studies, the review stated that loss of BAP1 staining is often seen in epithelioid and biphasic mesothelioma but is relatively uncommon in the sarcomatoid subtype. CDKN2A deletion is seen more often in the sarcomatoid subtype.
  • A cited study suggested MUC4 as a negative marker of sarcomatoid mesothelioma, to help distinguish it from lung sarcomatoid carcinoma.
  • In a cited study, INSM1 was positive in 94.9% of small cell lung carcinomas and 91.3% of large cell neuroendocrine carcinomas. The combined panel of three neuroendocrine markers was positive in 74.4% and 78.3%, respectively.
• The authors' conclusion: The author concluded that immunohistochemistry plays an essential role in distinguishing malignant mesothelioma, that choosing the right markers is essential, and that morphological, clinical and radiological features are also needed. More broadly, the author concluded that immunohistochemistry holds promise for improving lung cancer diagnosis and treatment.

Topics

Medical terms in this study, explained in our Lexicon: Immunohistochemistry, Lung Cancer, Biomarker, Adenocarcinoma, Squamous Cell Carcinoma, ROS1, EGFR, PD-L1.

Related studies

• Application of immunohistochemistry in the diagnosis of epithelioid mesothelioma: a review and update — N.G. Ordóñez (2013)
• Role of immunohistochemistry in differentiating epithelial mesothelioma from adenocarcinoma. Review and update — N.G. Ordóñez (1999)
• MTAP immunohistochemistry is an accurate and reproducible surrogate for CDKN2A fluorescence in situ hybridization in diagnosis of malignant pleural mesothelioma — D.B. Chapel, J.J. Schulte, et al. (2020)
• Immunohistochemical detection of MTAP and BAP1 protein loss for mesothelioma diagnosis: Comparison with 9p21 FISH and BAP1 immunohistochemistry — T. Hida, M. Hamasaki, et al. (2017)
• Application of immunohistochemistry in diagnosis and management of malignant mesothelioma — D.B. Chapel, J.J. Schulte, et al. (2020)
• Utility of BAP1 Immunohistochemistry and p16 (CDKN2A) FISH in the Diagnosis of Malignant Mesothelioma in Effusion Cytology Specimens — H.C. Hwang, B.S. Sheffield, et al. (2016)

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