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. Copyright Â
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 cancerpatients 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. Copyright Â
Authors: Emily S Bell; Pragya Shah; Noam Zuela-Sopilniak; Dongsung Kim; Alice-Anais Varlet; Julien L P Morival; Alexandra L McGregor; Philipp Isermann; Patricia M Davidson; Joshua J Elacqua; Jonathan N Lakins; Linda Vahdat; Valerie M Weaver; Marcus B Smolka; Paul N Span; Jan Lammerding Journal: Oncogene Date: 2022-07-27 Impact factor: 8.756
Authors: Diego J Martinel Lamas; Jorge E Cortina; Clara Ventura; Helena A Sterle; Eduardo Valli; Karina B Balestrasse; Horacio Blanco; Graciela A Cremaschi; Elena S Rivera; Vanina A Medina Journal: Cancer Biol Ther Date: 2015 Impact factor: 4.742
Authors: Yuhua Wang; Ram Naresh Pandey; Kaushik Roychoudhury; David Milewski; Tanya V Kalin; Sara Szabo; Joseph G Pressey; Rashmi S Hegde Journal: Mol Cancer Ther Date: 2021-03-01 Impact factor: 6.009