Phospho-histone H2AX is a diagnostic and prognostic marker for epithelial ovarian cancer

Int J Clin Exp Pathol. 2015 May 1;8(5):5597-602. eCollection 2015.

Abstract

Background: Histone H2AX phosphorylation is a sensitive marker for DSB which contributes to both genomic instability and cancer treatment. Monitoring its formation may be a sensitive means to monitor cancer progression and treatment effect.

Objective: To define the role of phospho-H2AX (pH2AX) expression in development and prognosis of epithelial ovarian cancer (EOC).

Methods: The expression of pH2AX in 87 EOC samples and 28 samples of normal ovarian tissues were examined by immunohistochemistry (IHC). The results were semi-quantitatively scored and analyzed by chi-square test. The overall survival time (OS) and disease free interval (DFI) were collected by follow-up and analyzed by Kaplan-Meier analysis.

Results: The expression level of pH2AX protein in EOC were higher than that in normal tissues (P<0.001). Among the sensitive cases, high expression of pH2AX was found in 53.2% cases while for resistant cases, high expression rate was 80% (P=0.025). However, pH2AX expression was not significantly correlated with age, histopathological type, tumor differentiation, lymph node metastasis or FIGO stages. Kaplan-Meier analysis found that DFI was negatively correlated with the pH2AX expression, where higher expression of pH2AX resulted in shorter DFI while no OS difference was detected in our study.

Conclusion: pH2AX may be used to detect EOC at an early stage and identify women at higher risk for relapse.

Keywords: Histone H2AX; Kaplan-Meier analysis; disease free interval; epithelial ovarian cancer; immunohistochemistry; overall survival.

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Carcinoma, Ovarian Epithelial
  • Case-Control Studies
  • Cell Differentiation
  • Chi-Square Distribution
  • Disease Progression
  • Disease-Free Survival
  • Early Detection of Cancer / methods
  • Female
  • Histones / analysis*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / chemistry*
  • Neoplasms, Glandular and Epithelial / mortality
  • Neoplasms, Glandular and Epithelial / secondary
  • Neoplasms, Glandular and Epithelial / therapy
  • Ovarian Neoplasms / chemistry*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / therapy
  • Phosphorylation
  • Predictive Value of Tests
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • H2AX protein, human
  • Histones