Global assessment of IRF8 as a novel cancer biomarker.

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From: Human Pathology(Vol. 122)
Publisher: Elsevier B.V.
Document Type: Report
Length: 420 words

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Abstract :

Keywords Myeloid sarcoma; Blastic plasmacytoid dendritic neoplasms; IRF8; Cancer tissue microarrays Highlights * Novel marker IRF8 detects myeloid sarcomas and blastic plasmacytoid dendritic cell neoplasms. * IRF8 is negative in other solid tumors in differential, as correlated with TCGA data. * Monocytic blasts are positive for IRF8 as opposed to blasts of granulocytic differentiation. Summary Interferon regulatory factor 8 (IRF8) is a member of the IRF family that is specific to the hematopoietic cell and is involved in regulating the development of human monocytic and dendritic-lineage cells, as well as B-cells. Because its utility as a sensitive and specific monoblast marker in the context of acute monocytic leukemias has been recently demonstrated, we hypothesized that it may also be useful as a novel immunohistochemical marker in myeloid sarcomas and blastic plasmacytoid dendritic cell neoplasms (BPDCNs) with respect to their differential diagnoses. In this retrospective study, we analyzed the IHC expression pattern of IRF8 in 385 patient samples across 30 types of cancers, referenced to their mRNA expression data available through The Cancer Genome Atlas. In addition, we assessed IRF8 in 35 myeloid sarcomas and 15 BPDCNs. Twenty-four of 35 cases of myeloid sarcomas (68.5%) showed positivity for IRF8, with six cases (17.1%) demonstrating IRF8 expression in the absence of CD34 and MPO. All 15 of 15 BPDCNs (100%) showed strong uniform expression of IRF8 and were occasionally more definitive than CD123. IRF8 was negative in all desmoplastic small round cell tumors, Ewing sarcomas, synovial sarcomas, and undifferentiated pleomorphic sarcomas, as well as all epithelial malignancies tested except for 2 triple negative breast cancers that showed subset weak staining. In conclusion, IRF8 is a novel marker helpful in identifying extranodal hematopoietic tumors that can otherwise be difficult to diagnose given the broad differential diagnoses and frequent loss of more common lineage-defining markers. Author Affiliation: (a) Department of Pathology, Yale New-Haven Hospital, Yale School of Medicine, New Haven, CT, 06510, USA (b) Department of Pathology and Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA (c) Department of Pathology, Brigham and Women's Hospital, Boston, MA, 02115, USA * Corresponding author. 310 Cedar Street, BML116, New Haven, CT 06510, USA. Article History: Received 6 December 2021; Revised 15 January 2022; Accepted 17 January 2022 (footnote)[white star] Disclosures: None. (footnote)1 These authors contributed equally to this work. Byline: Daniel C. McQuaid, BS (a), Gauri Panse, MD (a), Wei-Lien Wang, MD (b), Geraldine S. Pinkus, MD (c), Samuel G. Katz, MD, PhD [] (a,**,1), Mina L. Xu, MD [] (a,*,1)

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Gale Document Number: GALE|A698875463