Immunostaining in lung cancer for the clinician. Commonly used markers for differentiating primary and metastatic pulmonary tumors

Our plain-English summary of Immunostaining in lung cancer for the clinician. Commonly used markers for differentiating primary and metastatic pulmonary tumors, by J.M. Carney, A.M. Kraynie, V.L. Roggli (Annals of the American Thoracic Society, 2015).

The study

• Authors: J.M. Carney, A.M. Kraynie, V.L. Roggli
• Journal: Annals of the American Thoracic Society
• Published: 2015;12(3):429-35
• Type of article: Review
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Immunohistochemical stains have become invaluable for the diagnosis of pulmonary malignancies (both primary and metastatic), particularly given the small size of transbronchial and endobronchial biopsies and the increasing need to conserve tissue for molecular studies. There are many panels of immunostains currently available to help differentiate between common types of pulmonary malignancies. It is the purpose of this review to summarize some of the most commonly used immunostains for the distinction of primary pulmonary malignancies from one another in areas with histological overlap and for distinguishing primary pulmonary malignancies from other cancers with which they may be confused. These include differentiating between poorly differentiated adenocarcinoma and poorly differentiated squamous cell carcinoma, small cell/large cell neuroendocrine carcinoma and basaloid carcinoma, and primary and metastatic adenocarcinoma involving the lung. In addition, we address the distinction between mesothelioma and pulmonary adenocarcinoma. Pitfalls in the use of these markers are also addressed. Although not aiming to be comprehensive, this review aims to guide and influence common practice by furthering the clinician's knowledge on using immunohistochemical stains for characterization of pulmonary neoplasms. This summary of frequently used immunohistochemical stains can provide usefulness by allowing accurate characterization of pulmonary tumors, thereby allowing for conservation of tissue for additional molecular testing.

In plain English

This article was a review, not a new study. The authors summarized published research and guidelines on common immunostains, which are laboratory stains that help pathologists tell tumor types apart on small biopsies. It covered lung cancer types that can look alike, cancer that started in the lung versus cancer that spread there, and malignant mesothelioma versus lung adenocarcinoma. For epithelioid mesothelioma, it listed calretinin, CK5/6, WT-1 and D2-40 as positive markers and TTF-1 and CEA as markers of lung adenocarcinoma. It noted that guidelines recommend using two positive and two negative stains. For sarcomatoid mesothelioma, the authors wrote that in their experience a broad-spectrum keratin stain is the most useful marker, positive in more than 90% of cases. The authors stated that no stain is 100% sensitive or specific, and that stains must be read alongside the tissue's appearance and the clinical history. They concluded that small biopsies call for limited stain panels, to save tissue for molecular testing, and for close teamwork between pathologist and clinician. The article did not address 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: Narrative review of published studies and guidelines on immunohistochemical stains; the authors state it is not comprehensive
• Who was studied: No study population of its own; the review summarized published immunostaining studies, textbook chapters and consensus guidelines on lung tumors, metastatic cancers in the lung, and mesothelioma
• Main results:
  • For telling lung adenocarcinoma from squamous cell carcinoma, the review described a frequently used panel of TTF-1, CK7, CK5/6, and p40 or p63
  • The review stated that a panel of 34βE12 plus neuroendocrine markers allows basaloid carcinoma to be distinguished from small cell carcinoma and large cell neuroendocrine carcinoma
  • Citing Pavlisko and Sporn's work on 366 cases of epithelioid mesothelioma, the review reported that calretinin, CK5/6, WT-1 and D2-40 stained epithelial or biphasic pleural mesothelioma with greater than 90% sensitivity
  • Citing guidelines, the review stated that TTF-1 is positive in 75-85% of pulmonary adenocarcinomas and is not expressed in mesotheliomas
  • Current guidelines for diagnosing malignant mesothelioma, as cited, recommend two positive and two negative immunostains
  • In the authors' experience, a broad-spectrum antikeratin stain is the single most useful marker for sarcomatoid mesothelioma and is positive in more than 90% of cases
  • In sarcomatoid mesothelioma, the review reported D2-40 positive in just over half and calretinin in just under half of cases; cytokeratin staining does not separate sarcomatoid lung carcinoma from sarcomatoid mesothelioma
  • Cited studies reported GATA-3, a breast cancer marker, in 23% of epithelioid mesotheliomas and in up to 58% of mesotheliomas (epithelioid and sarcomatoid), showing overlap between markers
• The authors' conclusion: The authors concluded that a limited stain panel should be used on small biopsies to conserve tissue for molecular studies, and that pathologists and clinicians should communicate closely
• Limitations the authors state:
  • No immunohistochemical test is 100% sensitive or specific
  • Laboratory protocols and antibodies can vary significantly between laboratories
  • The review does not aim to be comprehensive
  • Markers must be interpreted together with the tumor's appearance and the clinical history

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Adenocarcinoma, Squamous Cell Carcinoma, Carcinoma, Mesothelioma, Neoplasm, Molecular Profiling.

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)
• Wilms tumor 1/cytokeratin dual-color immunostaining reveals distinctive staining patterns in metastatic melanoma, metastatic carcinoma, and mesothelial cells in pleural fluids: an effective first-line test for the workup of malignant effusions — J.R. Conner, E.S. Cibas, et al. (2014)
• CAMTA1 immunostaining is not useful in differentiating epithelioid hemangioendothelioma from its potential mimickers — Z. Yusıflı, K. Kösemehmetoğlu (2014)
• E-cadherin, E-selectin and vascular cell adhesion molecule: immunohistochemical markers for differentiation between mesothelioma and metastatic pulmonary adenocarcinoma? — A.M. Müller, A. Weichert, et al. (2002)
• CD24: a potential new marker in differentiating malignant mesothelioma from pulmonary adenocarcinoma — D.J. Pinato, P. Nya, et al. (2013)
• BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations — M. Cigognetti, S. Lonardi, et al. (2015)

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