DNA damage marker phosphorylated histone H2AX is a potential predictive marker for progression of epithelial dysplasia of the oral cavity

Leung, E. Y. , McMahon, J. D., McLellan, D. R., Syyed, N., McCarthy, C. E., Nixon, C., Orange, C., Brock, C., Hunter, K. D. and Adams, P. D. (2017) DNA damage marker phosphorylated histone H2AX is a potential predictive marker for progression of epithelial dysplasia of the oral cavity. Histopathology, 71(4), pp. 522-528. (doi: 10.1111/his.13260) (PMID:28543539)

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

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Orange, Miss Clare and Nixon, Mr Colin and McLellan, Dr Douglas and Leung, Dr Elaine and Adams, Professor Peter and Hunter, Dr Keith and McMahon, Dr Jeremy and Reid, Mrs Claire
• Authors: Leung, E. Y., McMahon, J. D., McLellan, D. R., Syyed, N., McCarthy, C. E., Nixon, C., Orange, C., Brock, C., Hunter, K. D., and Adams, P. D.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
• Journal Name: Histopathology
• Publisher: Wiley
• ISSN: 0309-0167
• ISSN (Online): 1365-2559
• Published Online: 19 May 2017
• Copyright Holders: Copyright © 2017 John Wiley & Sons Ltd.
• First Published: First published in Histopathology 71(4):522-528
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher.