F Rojo1, J García-Parra2, S Zazo3, I Tusquets4, J Ferrer-Lozano5, S Menendez2, P Eroles5, C Chamizo3, S Servitja4, N Ramírez-Merino6, F Lobo6, B Bellosillo7, J M Corominas8, J Yelamos9, S Serrano10, A Lluch11, A Rovira2, J Albanell12. 1. 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. 2. Cancer Research Program, IMIM (Hospital del Mar Research Institute), Barcelona; Medical Oncology Department, Hospital del Mar, Barcelona. 3. Department of Pathology, IIS-Fundación Jiménez Díaz, Madrid. 4. Medical Oncology Department, Hospital del Mar, Barcelona. 5. Department of Oncology and Hematology, Hospital Clinico Universitario, Valencia. 6. Department of Oncology, IIS-Fundación Jiménez Díaz, Madrid. 7. Department of Pathology, Hospital del Mar, Barcelona. 8. 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. 9. Cancer Research Program, IMIM (Hospital del Mar Research Institute), Barcelona; Immunology Department, Hospital del Mar, Barcelona. 10. Department of Pathology, Hospital del Mar, Barcelona; Department of Medicine, Autonomous University of Barcelona, Barcelona. 11. Department of Oncology and Hematology, Hospital Clinico Universitario, Valencia; Department of Medicine, Valencia Central University, Valencia, Spain. 12. 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.
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. PATIENTS AND 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.
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. PATIENTS AND 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: Susanne Kossatz; Brandon Carney; Melanie Schweitzer; Giuseppe Carlucci; Vesselin Z Miloushev; Uday B Maachani; Prajwal Rajappa; Kayvan R Keshari; David Pisapia; Wolfgang A Weber; Mark M Souweidane; Thomas Reiner Journal: Cancer Res Date: 2017-01-20 Impact factor: 12.701
Authors: Giuseppe Carlucci; Brandon Carney; Christian Brand; Susanne Kossatz; Christopher P Irwin; Sean D Carlin; Edmund J Keliher; Wolfgang Weber; Thomas Reiner Journal: Mol Imaging Biol Date: 2015-12 Impact factor: 3.488
Authors: Brandon Carney; Giuseppe Carlucci; Beatriz Salinas; Valentina Di Gialleonardo; Susanne Kossatz; Axel Vansteene; Valerie A Longo; Alexander Bolaender; Gabriela Chiosis; Kayvan R Keshari; Wolfgang A Weber; Thomas Reiner Journal: Mol Imaging Biol Date: 2016-06 Impact factor: 3.488