title: Nuclear PARP-1 protein overexpression is associated with poor overall survival in early breast cancer.
abstract: BACKGROUND
  Poly(ADP-ribose)polymerase-1 (PARP-1) is a highly promising novel target in breast cancer. However, the expression of PARP-1 protein in breast cancer and its associations with outcome are yet poorly characterized.
  
  
  METHODS
  Quantitative expression of PARP-1 protein was assayed by a specific immunohistochemical signal intensity scanning assay in a range of normal to malignant breast lesions, including a series of patients (N = 330) with operable breast cancer to correlate with clinicopathological factors and long-term outcome.
  
  
  RESULTS
  PARP-1 was overexpressed in about a third of ductal carcinoma in situ and infiltrating breast carcinomas. PARP-1 protein overexpression was associated to higher tumor grade (P = 0.01), estrogen-negative tumors (P < 0.001) and triple-negative phenotype (P < 0.001). The hazard ratio (HR) for death in patients with PARP-1 overexpressing tumors was 7.24 (95% CI; 3.56-14.75). In a multivariate analysis, PARP-1 overexpression was an independent prognostic factor for both disease-free (HR 10.05; 95% CI 5.42-10.66) and overall survival (HR 1.82; 95% CI 1.32-2.52).
  
  
  CONCLUSIONS
  Nuclear PARP-1 is overexpressed during the malignant transformation of the breast, particularly in triple-negative tumors, and independently predicts poor prognosis in operable invasive breast cancer.
authors: Cancer Research Program, IMIM (Hospital del Mar Research Institute), Barcelona; Department of Pathology, Hospital del Mar, Barcelona; Department of Pathology, IIS-Fundación Jiménez Díaz, Madrid.
authors: F
authors: F
authors: Rojo
authors: Cancer Research Program, IMIM (Hospital del Mar Research Institute), Barcelona; Medical Oncology Department, Hospital del Mar, Barcelona.
authors: J
authors: J
authors: García-Parra
authors: Department of Pathology, IIS-Fundación Jiménez Díaz, Madrid.
authors: S
authors: S
authors: Zazo
authors: Medical Oncology Department, Hospital del Mar, Barcelona.
authors: I
authors: I
authors: Tusquets
authors: Department of Oncology and Hematology, Hospital Clinico Universitario, Valencia.
authors: J
authors: J
authors: Ferrer-Lozano
authors: Cancer Research Program, IMIM (Hospital del Mar Research Institute), Barcelona; Medical Oncology Department, Hospital del Mar, Barcelona.
authors: S
authors: S
authors: Menendez
authors: Department of Oncology and Hematology, Hospital Clinico Universitario, Valencia.
authors: P
authors: P
authors: Eroles
authors: Department of Pathology, IIS-Fundación Jiménez Díaz, Madrid.
authors: C
authors: C
authors: Chamizo
authors: Medical Oncology Department, Hospital del Mar, Barcelona.
authors: S
authors: S
authors: Servitja
authors: Department of Oncology, IIS-Fundación Jiménez Díaz, Madrid.
authors: N
authors: N
authors: Ramírez-Merino
authors: Department of Oncology, IIS-Fundación Jiménez Díaz, Madrid.
authors: F
authors: F
authors: Lobo
authors: Department of Pathology, Hospital del Mar, Barcelona.
authors: B
authors: B
authors: Bellosillo
authors: Cancer Research Program, IMIM (Hospital del Mar Research Institute), Barcelona; Department of Pathology, Hospital del Mar, Barcelona; Department of Medicine, Autonomous University of Barcelona, Barcelona.
authors: J M
authors: JM
authors: Corominas
authors: Cancer Research Program, IMIM (Hospital del Mar Research Institute), Barcelona; Immunology Department, Hospital del Mar, Barcelona.
authors: J
authors: J
authors: Yelamos
authors: Department of Pathology, Hospital del Mar, Barcelona; Department of Medicine, Autonomous University of Barcelona, Barcelona.
authors: S
authors: S
authors: Serrano
authors: Department of Oncology and Hematology, Hospital Clinico Universitario, Valencia; Department of Medicine, Valencia Central University, Valencia, Spain.
authors: A
authors: A
authors: Lluch
authors: Cancer Research Program, IMIM (Hospital del Mar Research Institute), Barcelona; Medical Oncology Department, Hospital del Mar, Barcelona.
authors: A
authors: A
authors: Rovira
authors: Cancer Research Program, IMIM (Hospital del Mar Research Institute), Barcelona; Medical Oncology Department, Hospital del Mar, Barcelona; Department of Medicine, Autonomous University of Barcelona, Barcelona. Electronic address: jalbanell@hospitaldelmar.cat.
authors: J
authors: J
authors: Albanell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D018450:Disease Progression; D004622:Embryo, Mammalian; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D034741:RNA, Small Interfering / Q000494:pharmacology; D016019:Survival Analysis; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D034741:RNA, Small Interfering; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases