ATM down-regulation is associated with poor prognosis in sporadic breast carcinomas

Author(s)

Bueno, R. C. ^{[1, 2]} ; Canevari, R. A. ^[3] ; Villacis, R. A. R. ^{[1, 2]} ; Domingues, M. A. C. ^[4] ; Caldeira, J. R. F. ^[5] ; Rocha, R. M. ^[6] ; Drigo, S. A. ^{[1, 2]} ; Rogatto, S. R. ^{[1, 2]}

Affiliation

^[1] Sao Paulo State Univ, Dept Urol, NeoGene Lab, BR-18618970 Botucatu, SP - Brazil

^[2] AC Camargo Canc Ctr, Sao Paulo - Brazil

^[3] Paraiba Valley Univ, IP&D, Inst Res & Dev, Lab Biomed Vibrat Spect LEVB, Sao Jose Dos Campos - Brazil

^[4] Sao Paulo State Univ, Dept Pathol, BR-18618970 Botucatu, SP - Brazil

^[5] Amaral Carvalho Hosp, Dept Senol, Jau - Brazil

^[6] AC Camargo Canc Ctr, Dept Pathol, Sao Paulo - Brazil

• Document type: Journal article
• Source: Annals of Oncology; v. 25, n. 1, p. 69-75, JAN 2014.
• Web of Science Citations: 29

Abstract

Background: Ataxia telangiectasia-mutated (ATM) gene downexpression has been reported in sporadic breast carcinomas (BC); however, the prognostic value and mechanisms of ATM deregulation remain unclear. Patients and methods: ATM and miRNAs (miR-26a, miR-26b, miR-203, miR-421, miR-664, miR-576-5p and miR-18a) expression levels were evaluated by quantitative real-time PCR (RT-qPCR) in 52 BC and 3 normal breast samples. ATM protein expression was assessed by immunohistochemistry in 968 BC and 35 adjacent normal breast tissues. ATM copy number alteration was detected by array comparative genomic hybridization (aCGH) in 42 tumours. Results: Low ATM levels were associated with tumour grade. Absence of ATM protein expression was associated with distant metastasis (P < 0.001), reduced disease-free survival (DFS, P < 0.001) and cancer-specific survival (CSS, P < 0.001). Multivariate analysis indicated ATM protein expression as an independent prognostic marker for DFS (P = 0.001, HR = 0.579) and CSS (P = 0.001, HR = 0.554). ATM copy number loss was detected in 12% of tumours and associated with lower mRNA levels. miR-421 over-expression was detected in 36.5% of cases which exhibit lower ATM transcript levels (P = 0.075, r = -0.249). Conclusions: The data suggest that ATM protein expression is an independent prognostic marker in sporadic BC. Gene copy number loss and miR-421 over-expression may be involved in ATM deregulation in BC. (AU)

• FAPESP's process: 08/57887-9 - National Institute of Oncogenomics
• Grantee: Luiz Paulo Kowalski
• Support Opportunities: Research Projects - Thematic Grants