Leung, E.Y., McMahon, J.D., McLellan, D. et al. (7 more authors) (2017) DNA damage marker γH2AX is a potential predictive marker for progression of epithelial dysplasia of the oral cavity. Histopathology, 71 (4). pp. 522-528. ISSN 0309-0167
Abstract
AIMS: To evaluate the relationships between immunohistochemical markers related to cellular senescence, cell proliferation and histological grade of epithelial dysplasia of the oral cavity (OD). In addition, the predictive value of these markers for progression of OD was assessed.
METHODS: Retrospective immunohistochemical analyses were performed on 86 formalin fixed and paraffin embedded specimens of OD and oral squamous cell carcinoma (OSCC) for Ki67, γH2AX, p53, p16, H3K9me3 and CycD1. Three separate areas representing the highest severity of OD on each slide were digitally annotated by two independent pathologists. Mean automated histoscores of the selected markers were generated and compared to that of age-matched healthy controls (n=24). Follow-up data of OD was retrieved and anonymised by a clinical team member and linked using unique participant identifiers. The median follow-up was 10.9 years (interquartile range: 10.1-11.5).
RESULTS: Ki67 (p<0.0001), γH2AX (p=0.03) and p53 (p=0.04) were significantly increased with higher histological grade of OD. γH2AX (p=0.03), but not histological grade of OD (p=0.73), was prospectively associated with disease progression. Using the median histoscore for γH2AX (median histoscore = 17) as a cut-off, histoscore≥17 was associated with an increased risk of disease progression (HR=3.15, 95%CI 1.41-7.39, p=0.0064).
CONCLUSIONS: Although proliferation marker Ki67, DNA damage/checkpoint markers γH2AX and p53 were increased in higher grade of OD, only γH2AX was predictive of disease progression. These observations may reflect the role of DNA replicative stress in the transformation from OD to OSCC. Larger studies should evaluate whether γH2AX can be used as a predictive marker of OD.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 John Wiley & Sons Ltd. This is the peer reviewed version of the following article: Leung, E., McMahon, J., McLellan, D., Syyed, N., McCarthy, C., Nixon, C., Orange, C., Brock, C., Hunter, K. and Adams, P. D. (), DNA damage marker γH2AX is a potential predictive marker for progression of epithelial dysplasia of the oral cavity. Histopathology. , which has been published in final form at https://doi.org/10.1111/his.13260. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. |
Keywords: | oral cavity; neoplasm; carcinoma in situ; cellular senescence; biomarkers; immunohistochemistry |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Clinical Dentistry (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 08 Jun 2017 09:10 |
Last Modified: | 31 Jul 2023 15:07 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1111/his.13260 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:117337 |