Loss of FANCD2 and related proteins may predict malignant transformation in oral epithelial dysplasia

Ho, Michael W, Ryan, Mark P, Gupta, Juhi ORCID: 0000-0002-8292-9846, Triantafyllou, Asterios, Risk, Janet M ORCID: 0000-0002-8770-7783, Shaw, Richard J ORCID: 0000-0002-5157-4042 and Wilson, James B (2022) Loss of FANCD2 and related proteins may predict malignant transformation in oral epithelial dysplasia. ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY, 133 (4). pp. 377-387.

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Abstract

<h4>Objective</h4>Predicting malignant transformation (MT) in oral epithelial dysplasia (OED) is challenging. The higher rate of MT reported in nonsmokers suggests an endogenous etiology in oncogenesis. We hypothesize that loss of FANCD2 and associated proteins could influence genomic instability and MT in the absence of environmental carcinogens.<h4>Study design</h4>Longitudinal archival samples were obtained from 40 individuals with OED: from diagnosis to the most recent review in 23 patients with stable OED or until excision of the squamous cell carcinoma in 17 patients with unstable OED undergoing MT. Histopathological reassessment, immunohistochemistry for FANCD2, and Western blotting for phosphorylation/monoubiquitylation status of ATR, CHK1, FANCD2, and FANCG were undertaken on each tissue sample.<h4>Results</h4>Decreased expression of FANCD2 was observed in the diagnostic biopsies of OED lesions that later underwent MT. Combining the FANCD2 expression scores with histologic grading more accurately predicted MT (P = .005) than histology alone, and it correctly predicted MT in 10 of 17 initial biopsies. Significantly reduced expression of total FANCD2, pFANCD2, pATR, pCHK-1, and pFANCG was observed in unstable OED.<h4>Conclusions</h4>There is preliminary evidence that defects in the DNA damage sensing/signaling/repair cascade are associated with MT in OED. Loss of expression of FANCD2 protein in association with a higher histologic grade of dysplasia offered better prediction of MT than clinicopathologic parameters alone.

Item Type:	Article
Uncontrolled Keywords:	Humans, Carcinoma, Squamous Cell, Mouth Neoplasms, Cell Transformation, Neoplastic, Precancerous Conditions, Hyperplasia, Fanconi Anemia Complementation Group D2 Protein
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	09 Jul 2021 08:54
Last Modified:	18 Jan 2023 21:36
DOI:	10.1016/j.oooo.2021.07.001
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3129403