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Ataxia Telangiectasia Mutated Protein Loss and Benefit From Oxaliplatin-based Chemotherapy in Colorectal Cancer
- Source :
- Clinical Colorectal Cancer. 17:280-284
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Background Loss of ataxia telangiectasia mutated (ATM), a key protein regulating DNA repair signaling, has been suggested to increase sensitivity to DNA damaging agents. We conducted a study analyzing the loss of ATM protein expression in colorectal cancer and correlated this with clinical outcomes. Materials and Methods The clinical outcomes data and tumor samples from metastatic colorectal cancer patients referred to the Royal Marsden Hospital Drug Development Unit (United Kingdom) from 2012 to 2016 and providing consent for a molecular characterization study were analyzed. Immunohistochemistry (IHC) slides were assessed by a pathologist for nuclear staining intensity of ATM and semiquantitatively scored. ATM loss was defined as a nuclear H-score of ≤ 10. Results Of 223 colorectal cancer samples, ATM IHC loss was identified in 17 (8%). ATM loss was independent of the RAS and RAF mutational status. ATM loss was associated with superior overall survival after first-line oxaliplatin-based therapy (49 vs. 32 months; hazard ratio [HR], 2.52) but not with irinotecan-based therapy (24 vs. 33 months; HR, 0.72). ATM loss was not prognostic for survival from the diagnosis (50 vs. 44 months; HR, 1.43). Conclusion ATM could be considered a biomarker for the development of novel DNA repair targeting agents and treatment of colorectal cancer.
- Subjects :
- Adult
Male
0301 basic medicine
Oncology
medicine.medical_specialty
DNA Repair
DNA repair
Colorectal cancer
medicine.medical_treatment
Ataxia Telangiectasia Mutated Proteins
Young Adult
03 medical and health sciences
0302 clinical medicine
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
Biomarkers, Tumor
Humans
Medicine
Aged
Retrospective Studies
Aged, 80 and over
Chemotherapy
business.industry
Liver Neoplasms
Hazard ratio
Gastroenterology
Middle Aged
Prognosis
medicine.disease
Oxaliplatin
Gene Expression Regulation, Neoplastic
Survival Rate
Irinotecan
030104 developmental biology
030220 oncology & carcinogenesis
Biomarker (medicine)
Immunohistochemistry
Female
Colorectal Neoplasms
business
Follow-Up Studies
medicine.drug
Subjects
Details
- ISSN :
- 15330028
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- Clinical Colorectal Cancer
- Accession number :
- edsair.doi.dedup.....a5b111c62318a4ac33165846b3ed1526