Constitutive expression of γ-H2AX has prognostic relevance in triple negative breast cancer

Radiother Oncol. 2011 Oct;101(1):39-45. doi: 10.1016/j.radonc.2011.07.009. Epub 2011 Aug 15.


Background and purpose: Constitutive γ-H2AX expression might indicate disruption of the DNA damage repair pathway, genomic instability, or shortened telomeric ends. Here, we quantified expression of endogenous γ-H2AX and its downstream factor 53BP1 in a large number of breast cancer cell lines (n=54) and a node-negative breast cancer cohort that had not received adjuvant systemic treatment (n=122).

Materials and methods: Formalin fixed paraffin embedded breast cancer cell lines and tumors were immunohistochemically analyzed for γ-H2AX and 53BP1 expression, and related to cell line, patient and tumor characteristics and to disease progression.

Results: In breast cancer cell lines, γ-H2AX positivity was associated with the triple negative/basal like subgroup (p=0.005), and with BRCA1 (p=0.011) or p53 (p=0.053) mutations. Specifically in triple negative breast cancer patients a high number of γ-H2AX foci indicated a significantly worse prognosis (p=0.006 for triple negative vs. p=0.417 for estrogen receptor (ER), progesterone receptor (PR) or HER2 positive patients). A similar association with disease progression was found for 53BP1. In a multivariate analysis with tumor size, grade, and triple negativity, only the interaction between triple negativity and γ-H2AX remained significant (p=0.002, Hazard Ratio=6.77, 95% CI=2.07-22.2).

Conclusions: Constitutive γ-H2AX and 53BP1 staining reveals a subset of patients with triple negative breast tumors that have a significantly poorer prognosis.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Biopsy, Needle
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cohort Studies
  • DNA Damage / genetics
  • DNA Repair / genetics
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genetic Predisposition to Disease*
  • Histones / metabolism*
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Progesterone / metabolism
  • Survival Analysis
  • Tissue Embedding
  • Tumor Suppressor p53-Binding Protein 1


  • Biomarkers, Tumor
  • H2AX protein, human
  • Histones
  • Intracellular Signaling Peptides and Proteins
  • Receptors, Progesterone
  • TP53BP1 protein, human
  • Tumor Suppressor p53-Binding Protein 1
  • Receptor, ErbB-2