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
. 2022 Jul;481(1):23-29.
doi: 10.1007/s00428-022-03336-1. Epub 2022 May 16.

5-hmC loss is another useful tool in addition to BAP1 and MTAP immunostains to distinguish diffuse malignant peritoneal mesothelioma from reactive mesothelial hyperplasia in peritoneal cytology cell-blocks and biopsies

Ziyad Alsugair  1 , Vahan Kepenekian  2   3   4 , Tanguy Fenouil  5 , Olivier Glehen  2   3   4 , Laurent Villeneuve  3   4   6   7 , Sylvie Isaac  1   3   4 , Juliette Hommell-Fontaine  1   3   4 , Nazim Benzerdjeb  8   9   10
Affiliations

5-hmC loss is another useful tool in addition to BAP1 and MTAP immunostains to distinguish diffuse malignant peritoneal mesothelioma from reactive mesothelial hyperplasia in peritoneal cytology cell-blocks and biopsies

Ziyad Alsugair et al. Virchows Arch. 2022 Jul.

Abstract

The differentiation between reactive mesothelial hyperplasia (RMH) and diffuse malignant peritoneal mesothelioma (DMPM) is challenging especially when applied on peritoneal small samples. The use of BRCA-associated protein 1 (BAP1) and methylthioadenosine phosphorylase (MTAP) immunostains is familiar to identify malignant mesothelial proliferation. Recently, nuclear 5-hydroxymethylcytosine (5-hmC) was reported to be a new recognition tool of pleural mesothelial malignancy on surgical specimens. However, application of 5-hmC immunostaining has not yet studied in peritoneal specimens from small biopsies or cytology cell-blocks. The aim was to assess the diagnostic accuracy of this new marker combination to distinguish DMPM from RMH in biopsies and cell-blocks. Seventy-five cases were analyzed; among which, 38 were of cytological specimens including 6 RMH and 32 DMPM, and 37 tissue biopsies with 7 RMH and 30 DMPM. BAP1, MTAP, and 5-hmC immunostains were performed on all cases. RMH cases exhibited a retained staining with all immunostains. Among DMPM, BAP1 was lost in 71.8% of cytology cell-blocks and 66.7% of biopsies. MTAP was lost in 40.6% of cytology cell-blocks and 33.3% of biopsies. 5-hmC was lost in 40.6% of cytology cell-blocks and 30% of biopsies. The combination of BAP1, MTAP, and 5-hmC showed the best accuracy in differential diagnosis between RMH and DMPM (sensitivity = 0.84, specificity = 1 in cytology cell-blocks; sensitivity = 0.90, specificity = 1 in biopsy). The best diagnostic combination in peritoneal cytology effusion fluids and biopsies samples provided by BAP1, MTAP, and 5-hmC should be applied on a diagnostic step-wise algorithm by pathologists involved into the management of DMPM, because of their therapeutic implications.

Keywords: 5-hmC; Biomarker; Diffuse malignant peritoneal mesothelioma; Mesothelioma; Reactive mesothelial hyperplasia.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

References

    1. Attanoos RL, Griffin A, Gibbs AR (2003) The use of immunohistochemistry in distinguishing reactive from neoplastic mesothelium. A novel use for desmin and comparative evaluation with epithelial membrane antigen, p53, platelet-derived growth factor-receptor, P-glycoprotein and Bcl-2. Histopathology 43:231–238. https://doi.org/10.1046/j.1365-2559.2003.01686.x - DOI - PubMed
    1. Bruno R, Alì G, Fontanini G (2018) Molecular markers and new diagnostic methods to differentiate malignant from benign mesothelial pleural proliferations: a literature review. J Thorac Dis 10:S342–S352. https://doi.org/10.21037/jtd.2017.10.88 - DOI - PubMed - PMC
    1. Sheffield BS, Hwang HC, Lee AF et al (2015) BAP1 immunohistochemistry and p16 FISH to separate benign from malignant mesothelial proliferations. Am J Surg Pathol 39:977–982. https://doi.org/10.1097/PAS.0000000000000394 - DOI - PubMed
    1. Hida T, Hamasaki M, Matsumoto S et al (2017) Immunohistochemical detection of MTAP and BAP1 protein loss for mesothelioma diagnosis: comparison with 9p21 FISH and BAP1 immunohistochemistry. Lung Cancer 104:98–105. https://doi.org/10.1016/j.lungcan.2016.12.017 - DOI - PubMed
    1. Andrici J, Parkhill TR, Jung J et al (2016) Loss of expression of BAP1 is very rare in non-small cell lung carcinoma. Pathology 48:336–340. https://doi.org/10.1016/j.pathol.2016.03.005 - DOI - PubMed

MeSH terms

Substances

LinkOut - more resources