TY - JOUR
T1 - Constitutive expression of γ-H2AX has prognostic relevance in triple negative breast cancer
AU - Nagelkerke, Anika
AU - van Kuijk, Simon J A
AU - Sweep, Fred C G J
AU - Nagtegaal, Iris D
AU - Hoogerbrugge, Nicoline
AU - Martens, John W M
AU - Timmermans, Mieke A
AU - van Laarhoven, Hanneke W M
AU - Bussink, Johan
AU - Span, Paul N
N1 - Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
PY - 2011/10
Y1 - 2011/10
N2 - 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.
AB - 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.
U2 - 10.1016/j.radonc.2011.07.009
DO - 10.1016/j.radonc.2011.07.009
M3 - Article
C2 - 21840613
SN - 0167-8140
VL - 101
SP - 39
EP - 45
JO - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
JF - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
IS - 1
ER -
