Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Feb;82(3):385-392.
doi: 10.1111/his.14783. Epub 2022 Sep 5.

Hypothesis: HEG1 and claudin-4 staining will allow a diagnosis of epithelioid and biphasic mesothelioma versus non-small-cell lung carcinoma with only two stains in most cases

Andrew Churg  1   2 , Julia R Naso  1   2
Affiliations
Review

Hypothesis: HEG1 and claudin-4 staining will allow a diagnosis of epithelioid and biphasic mesothelioma versus non-small-cell lung carcinoma with only two stains in most cases

Andrew Churg et al. Histopathology. 2023 Feb.

Abstract

Separation of mesothelioma from metastatic carcinoma requires immunohistochemical support, with small batteries of stains recommended as a starting-point, but these numbers commonly expand to 10, 12 or more stains, a process that is not only expensive but frequently generates anomalous or confounding results, leading to even more stains. Here we review data on HEG1 clone SKM9-2, a new (now commercially available) mesothelioma marker and claudin-4, a broad-spectrum carcinoma marker, to ask whether these two stains are sufficient, by themselves, to separate mesotheliomas from non-small-cell lung (NSCLC) as well as other carcinomas. Data for HEG1, derived from four laboratories, showed membrane staining in 393 of 434 (91%) epithelioid/biphasic mesotheliomas and one of 360 (0.3%) NSCLC (sensitivity 91%, specificity 99.7%). Reports from seven laboratories evaluating claudin-4 in NSCLC showed positivity in 469 of 502 (93%) carcinomas and weak positivity in five of 463 (1.0%) epithelioid/biphasic mesotheliomas (sensitivity 93%, specificity 98.9%). Comparable results were found with carcinomas from other sites, except for serous and thyroid carcinomas, some of which react with HEG1 but are also positive for claudin-4. For sarcomatoid mesotheliomas, HEG1 sensitivity is modest and staining sometimes difficult to interpret. We hypothesise that the combination of HEG1 and claudin-4 immunostaining will potentially allow the separation of epithelioid/biphasic mesotheliomas from NSCLC carcinomas with high accuracy using only two immunostains in most cases. This combination will probably also work for carcinomas from most other sites, but more reports on HEG1 SKM9-2 staining of carcinomas other than NSCLC are needed. This approach would greatly simplify the diagnosis of mesothelioma.

Keywords: HEG1; claudin-4; mesothelioma; non-small-cell lung carcinoma.

PubMed Disclaimer

References

    1. WHO Classification of Tumors Editorial Board. Thoracic Tumors. Lyon: International Agency for Research on Cancer, 2021; 193-203.
    1. Husain AN, Colby TV, Ordóñez NG et al. Guidelines for pathologic diagnosis of malignant mesothelioma 2017 update of the consensus statement from the international mesothelioma interest group. Arch. Pathol. Lab. Med. 2018; 142; 89-108.
    1. Facchetti F, Lonardi S, Gentili F et al. Claudin 4 identifies a wide spectrum of epithelial neoplasms and represents a very useful marker for carcinoma versus mesothelioma diagnosis in pleural and peritoneal biopsies and effusions. Virchows Arch. 2007; 451; 669-680.
    1. Ordóñez NG. Value of claudin-4 immunostaining in the diagnosis of mesothelioma. Am. J. Clin. Pathol. 2013; 139; 611-619.
    1. Kleaveland B, Zheng X, Liu JJ et al. Regulation of cardiovascular development and integrity by the heart of glass-cerebral cavernous malformation protein pathway. Nat. Med. 2009; 15; 169-176.

LinkOut - more resources