ArticleBreast cancer research : BCR2015
Low ATM protein expression in malignant tumor as well as cancer-associated stroma are independent prognostic factors in a retrospective study of early-stage hormone-negative breast cancer.
Article in Breast cancer research : BCR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Expanding the therapeutic scope of PARP inhibitors in breast cancer: current indications and future directions.The Journal of clinical investigation · 2026Review
- Phosphorylated BLM peptide acts as an agonist for DNA damage response.Nucleic acids research · 2025Article
- Article
- The Cancer/Testis Antigen CT45A1 Promotes Transcription of OncogenicJournal of breast cancer · 2023Article
- Identification of New Molecular Biomarkers in Ovarian Cancer Using the Gene Expression Profile.Journal of clinical medicine · 2022Article
- Combining TMEM Doorway Score and MenaCancers · 2022Article
- Targeted Sequencing Revealed Distinct Mutational Profiles of Ocular and Extraocular Sebaceous Carcinomas.Cancers · 2021Article
- ATM kinase regulates tumor immunoreactions in lymphocyte-predominant breast cancer through modulation of NKG2D ligand and TNF cytokines on tumor cells.Medical molecular morphology · 2020Article
- Predictive and Prognostic Value of DNA Damage Response Associated Kinases in Solid Tumors.Frontiers in oncology · 2020Review
- Whole Genome Sequencing Identifies Key Genes in Spinal Schwannoma.Frontiers in genetics · 2020Article
- Expression Signatures of Cisplatin- and Trametinib-Treated Early-Stage Medaka Melanomas.G3 (Bethesda, Md.) · 2019Article
- Drug-Loaded Microbubbles Combined with Ultrasound for Thrombolysis and Malignant Tumor Therapy.BioMed research international · 2019Review
- Ataxia-Telangiectasia-Mutated Protein Expression as a Prognostic Marker in Adenoid Cystic Carcinoma of the Salivary Glands.Yonsei medical journal · 2018Article
- Sp1 phosphorylation by ATM downregulates BER and promotes cell elimination in response to persistent DNA damage.Nucleic acids research · 2018Article
- Hypoxia and Selective Autophagy in Cancer Development and Therapy.Frontiers in cell and developmental biology · 2018Review
- Loss of tumour-specific ATM protein expression is an independent prognostic factor in early resected NSCLC.Oncotarget · 2017Article
- Expression of PD-L1 and presence of CD8-positive T cells in pre-treatment specimens of locally advanced cervical cancer.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2017Article
- WSB1 overcomes oncogene-induced senescence by targeting ATM for degradation.Cell research · 2017Article
- Identification of the SUMO E3 ligase PIAS1 as a potential survival biomarker in breast cancer.PloS one · 2017Article
- Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe serine/threonine protein kinase ataxia telangiectasia mutated (ATM) is critical in maintaining genomic integrity. Upon DNA double-strand breaks, ATM phosphorylates key downstream proteins including p53 and BRCA1/2, thereby orchestrating complex signaling pathways involved in cell cycle arrest, DNA repair, senescence and apoptosis. Although sporadic mutation of ATM occurs rarely in breast cancer, the status of its protein expression and its clinical significance in breast cancer remain not well established. Our study was designed to investigate the influence of ATM protein in both tumor and cancer-associated stroma on clinical outcome in hormone-positive (HPBC) and hormone-negative (HNBC) early-stage breast cancer (EBC).
methodsTissue microarrays (TMAs), containing formalin-fixed, paraffin-embedded resected tumors from two cohorts of patients (HPBC cohort: n=130; HNBC cohort: n=168) diagnosed at the Tom Baker Cancer Centre, Calgary, Canada, were analyzed for ATM protein expression using fluorescence immunohistochemistry (IHC) and automated quantitative analysis (AQUA). ATM expression levels were measured within the tumor as a whole (tATM) as indicated by pan-cytokeratin expression, tumor nuclear compartment (nATM) as indicated by both DAPI and pan-cytokeratin-positive results, and cancer-associated stroma (csATM) as indicated by vimentin-positive and pan-cytokeratin-negative results. ATM expression levels within these compartments were correlated with clinical outcome.
resultsWhile tATM and nATM were significantly lower in tumors compared to normal breast epithelial tissues, csATM was significantly higher than the corresponding normal tissue compartment. In addition, the median expression level of both tATM and nATM were two- to threefold lower (P<0.001) in HNBC than in HPBC. In both HNBC and HPBC cohorts, patients with low tATM, nATM and csATM tumors had significantly poorer survival outcomes than those with a high tATM, nATM and csATM, but this effect was more pronounced in HNBC. A multivariate analysis demonstrates that these biomarkers predict survival independent of tumor size and lymph node status, but only in the HNBC cohort (P<0.001).
conclusionsLow ATM protein expression in both malignant tumor and stromal compartments likely contributes to the aggressive nature of breast cancer and is an independent prognostic factor associated with worse survival in HNBC patients.
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