title: The prognostic and predictive significance of PARP-1 in locally advanced breast cancer of Egyptian patients receiving neoadjuvant chemotherapy.
abstract: OBJECTIVE
  PARP-1 is a chromatin-associated enzyme that has a role in DNA repair and cell death. PARP-1 inhibitors are suggested therapy specifically for BRCA deficient breast carcinoma; however, their efficacy in sporadic breast cancer is under investigations. This study aimed to evaluate the PARP-1 in locally advanced breast cancer (LABC) cases to determine its predictive significance for outcome and response to neoadjuvant chemotherapy (NCT).
  
  
  METHODS
  This retrospective study was conducted on 84 LABC cases. Immunohistochemical expression of nuclear PARP-1 (nPARP-1) and cytoplasmic PARP-1 (cPARP-1) was evaluated in pretreatment needle core biopsies (NCBs). Results were correlated with clinicopathologic features, overall survival (OS), disease-free survival (DFS), and response to NCT in postoperative specimens.
  
  
  RESULTS
  High nPARP-1expression was observed in 64/84 (76%) of cases and was significantly associated with a lower lymph node stage (P=0.04). High cPARP-1 was observed in 40/84 (48%) of cases and it was significantly associated with lower lymph node stage (P=0.022) and lower tumor grade (P=0.050). High nPARP-1 expression was significantly associated with high cPARP-1 expression (P=0.005). Low cPARP-1 expression was associated with no response to chemotherapy in tumor site (P=0.021). According to the univariate survival analysis, high nPARP-1 and high cPARP-1 were significantly associated to longer OS (P=0.017 and P=0.019, respectively). High nPARP-1 but not cPARP-1 showed trend toward improved OS in multivariate Cox-regression analysis (P=0.053).
  
  
  CONCLUSIONS
  PARP-1 immunohistochemical expression is a marker of good prognosis and is predictive of response to NCT in LABC.
authors.affiliation: *Department of Pathology, Faculty of Medicine, Menoufia University, Menufia Departments of †Pathology ‡Oncology, National Cancer Institute, Cairo University, Cairo, Egypt §Department of Pathology, School of Medicine, The University of Nottingham, UK.
authors.forename: Hayam A
authors.initials: HA
authors.lastname: Aiad
authors.forename: Mona A H
authors.initials: MA
authors.lastname: Kandil
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: El-Tahmody
authors.forename: Iman L
authors.initials: IL
authors.lastname: Abulkheir
authors.forename: Fatma M
authors.initials: FM
authors.lastname: Abulkasem
authors.forename: Asma A
authors.initials: AA
authors.lastname: Elmansori
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Aleskandarany
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D004534:Egypt; D005260:Female; D006801:Humans; D008875:Middle Aged; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases