Expression of γ‐H2AX and patient prognosis in breast cancer cohort

Abstract

H2AX phosphorylation is a novel marker of DNA double-stranded breaks. In the present study, we assessed the γ-H2AX expression, its association with other clinicopathologic characteristics, and the prognosis in a cohort of 97 patients with breast cancer. Ninety-seven specimens of tumor tissue and 77 adjacent normal tissues from patients with breast cancer were examined. All patients underwent modified radical mastectomy or local tumor resection without lymph node dissection. γ-H2AX expression was assessed by standard immunohistochemistry.Patients were followed after surgery for a mean duration of 70.1 ± 18.7 months (range, 6-93 months). The γ-H2AX staining was positive in 27 (27.8%) patients. The positive rates of H2AX were 26.0% and 2.6% in tumor tissue and adjacent normal tissues, respectively. γ-H2AX positive status was negatively associated with TNM staging, with 24 positive cases (32.4%) in TNM staging I-II, while no positive cases in TNM staging III-IV (P = 0.026). Sixteen patients (16.5%) died during the followup. No significant association between γ-H2AX expression and patient survival was detected. The unadjusted HR (hazard ratio) for γ-H2AX positive was 0.84 (95% CI: 0.27, 2.60). In TNM staging subgroup analysis, death only occurred in γ-H2AX negative patients. Our study is the first study to demonstrate that expression of γ-H2AX is associated with TNM staging. Due to the small sample and limited follow-up time, we did not observe a significant association between γ-H2AX and patient survival. γ-H2AX expression could be a potential biomarker for cancer diagnosis and prediction, and further studies are in need.

A three layered histone epigenetics in breast cancer metastasis

“…ɣH2A.X serve as an signal that aids in the recruitment of DNA repairing machinery to the site of breakage [109]. Higher ɣH2A.X level has been reported in breast cancer patient samples and in triple negative breast cancer cells as well [110,111]. ɣH2A.X is also been reported to function via TRAF6-ATM-H2AX signaling axis mediated by Hypoxia inducible factor 1α (HIF1α) [108].…”

Early detection of urinary bladder carcinogens in rats by immunohistochemistry for γ-H2AX: a review from analyses of 100 chemicals

“…Therefore, immunostaining for γ-H2AX may be a useful tool to predict the genotoxicity and carcinogenicity of chemical substances 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 . The potential clinical applications of γ-H2AX immunostaining, such as prediction of cancer progression and response to radiotherapy, are also being investigated 20 , 21 . In bladder cancer, there may be a correlation between γ-H2AX formation in cancer cells and the risk of recurrence 22 , 23 , and γ-H2AX levels in peripheral leukocytes can be used as predictive factors for high-risk patients 24 , 25 .…”

DNA damage-related proteins in smokers and non-smokers with oral cancer

“…In recent years, the phosphorylated histone H2AX (γ-H2AX) marker has become a robust tool used to monitor DNA DSBs in cancer research and has been suggested to play a potential role in carcinogenesis and early cancer diagnosis. 12 Accordingly, studies have revealed a correlation between high γ-H2AX levels and worse prognosis and reduced disease-free survival in breast cancer, 28 ovarian cancer, 29 and hepatocellular carcinoma. 30 Interestingly, an association of H2AXpositive OSCC with reduced overall survival has been reported.…”