title: Nuclear PARP1 expression and its prognostic significance in breast cancer patients.
abstract: Poly(adenosine diphosphate [ADP]-ribose) polymerase 1 (PARP1) plays important roles in DNA damage response pathways and is often overexpressed in various human tumors. Currently, the use of PARP inhibitors for breast cancer (BC) therapy is the subject of debate, and there is an urgent need to understand much the expression and prognostic role of the PARP1 protein. The aim was to investigate the clinicopathological and prognostic significance of PARP1 in BC patients. The PARP1 and breast cancer susceptibility gene 1 (BRCA1) protein expressions were evaluated in 114 BCs by immunohistochemistry. Disease-free survival (DFS) and overall survival (OS) were determined based on the Kaplan-Meier method. Our results showed that nuclear PARP1 expression was significantly associated with peritumoral vascular invasion (P = 0.046), chemotherapeutic treatment (P = 0.026), oestrogen receptor (ER; P = 0.013), human epidermal growth factor receptor 2 (HER2; P = 0.003) and BRCA1 (P < 0.001) expression. Survival analyses showed a significant association with clinical outcome in the subgroup of ER-negative patients (P = 0.017 for DFS and P = 0.048 for OS) and in the subgroup of patients treated with chemotherapeutic agents (P = 0.042 for DFS and P = 0.046 for OS). A significant correlation was also found for DFS in patients characterized by tumors without peritumoral vascular invasion (P = 0.022). More importantly, multivariate analyses revealed that high nuclear PARP1 expression was associated with decreased DFS (P = 0.012) and OS (P = 0.026). In conclusion, PARP1 expression may be used as an independent prognostic factor in BC patients. In addition, this study demonstrated that high PARP1 expression may represent a marker of poorer prognosis both for patients with worse clinical outcome and in less aggressive clinical conditions.
authors.affiliation: Functional Biomorphology Laboratory, IRCCS Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco 65, 70124, Bari, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Mazzotta
authors.affiliation: Functional Biomorphology Laboratory, IRCCS Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco 65, 70124, Bari, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Partipilo
authors.affiliation: Molecular Genetic Laboratory, IRCCS Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco 65, 70124, Bari, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: De Summa
authors.affiliation: Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco 65, 70124, Bari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Giotta
authors.affiliation: Pathology Department, IRCCS Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco 65, 70124, Bari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Simone
authors.affiliation: Functional Biomorphology Laboratory, IRCCS Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco 65, 70124, Bari, Italy. a.mangia@oncologico.bari.it.
authors.forename: Anita
authors.initials: A
authors.lastname: Mangia
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D019313:BRCA1 Protein; D014408:Biomarkers, Tumor; D000071137:Poly (ADP-Ribose) Polymerase-1
keywords: BRCA1; Breast cancer; Immunohistochemistry; PARP1; Prognostic marker