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

Abstract

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.

Alterations in the expression of DNA damage response-related molecules in potentially preneoplastic oral epithelial lesions

“…Indeed, high γH2 AX immunohistochemical expression has been recently proposed as a potential predictive marker for progression of epithelial dysplasia to OSCC. 49 Of note, high γH2 AX expression in cancer rarely results in effective DNA repair, considering the high frequency of mutations in carcinogenesis. 50 Positive nuclear γH2 AX expression has been shown to correlate with a decreased overall survival in laryngeal SCC 51 and OSCC, 22 respectively.…”

Histone modifications in oral squamous cell carcinoma and oral potentially malignant disorders

“…Augmented H3K4me2 and H3K9me2 were noticed in OED and neoplasm compared to uninvolved epithelium (Piyathilake et al, ), whereas H3K9me3 displayed almost no change in the initiation and transformation of oral epithelial carcinogenesis (Leung et al, ). The incidence of HDAC2 positive staining increased from NOE through OED to OSCC (Chang et al, ).…”

“…Compared with hyperplasia and OSCC, γ‐H2A.X augmentation and the correlation between γ‐H2A.X abundance and dysplasia severity were demonstrated (Chou & Alawi, ). With tumor progression predictive ability, γ‐H2AX was also elevated in higher grades of OED (Leung et al, ). BMI1 accumulation was detected in both dysplastic and cancerous oral lesions (Kang et al, ).…”

Immunohistochemical assessment of chromatin licensing and DNA replication factor 1, geminin, and γ‐H2A.X in oral epithelial precursor lesions and squamous cell carcinoma

“…The 2017 WHO classification classifies oral epithelial dysplasia into low‐grade and high‐grade types and as oral potentially malignant disorders, including leukoplakia . Significant efforts have been made to identify biomarkers that can be used to predict the value of histological grading during the oncologic process through the epithelium, and molecules modulating the cell cycle may be essential for early diagnostic and prognostic evaluation …”

“…Cell proliferation follows an orderly progression through the cell cycle, which is governed by various molecules, and uncontrolled cell cycle progression caused by aberrant expression of regulatory molecules is correlated with oncogenesis . During early G 1 phase under the pre‐replication complex (pre‐RC) formed by the origin recognition complex, chromatin licensing and DNA replication factor 1 (CDT1) and cell division cycle 6 load the minichromosome maintenance complex (minichromosome maintenance proteins 2‐7).…”