title: Nuclear-cytoplasmic PARP-1 expression as an unfavorable prognostic marker in lymph node‑negative early breast cancer: 15-year follow-up.
abstract: PARP-1 plays an important role in DNA damage repair and maintaining genome integrity by repairing DNA single-strand breaks (SSBs) by base excision repair (BER). The aim of the present study was to examine the expression of PARP-1 in breast cancer (BC) patients and to assess the relationship between the subcellular localization of this protein and clinicopathological characteristics. The reactivity of PARP-1 was analyzed by immunohistochemistry in a homogeneous group of 83 stage II ductal BC patients with a 15-year follow-up. Immunostaining of PARP-1 was also evaluated in 4 human BC cell lines and resistance prediction profile for 11 anticancer agents was performed using 3 models of drug-resistant cell lines. Nuclear-cytoplasmic expression (NCE) was associated with shorter overall survival, which was not statistically significant during the 10-year follow-up but became statistically significant after 10 years of observation, during the 15-year follow-up (P=0.015). Analysis performed in subgroups of patients with (N+) and without (N-) nodal metastases showed that NCE was associated with poor clinical outcome in N- patients (P=0.017). Multivariate analysis confirmed a significant impact of NCE on unfavorable prognosis in N- early BC. The presence of PARP-1 NCE may be a new potential unfavorable prognostic factor in lymph node- negative early BC.
authors.affiliation: Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, 50-556 Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Donizy
authors.affiliation: Laboratory of Mammotomic Biopsy, 4th Military Hospital, 50-001 Wroclaw, Poland.
authors.forename: Grazyna
authors.initials: G
authors.lastname: Pietrzyk
authors.affiliation: Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, 50-556 Wroclaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Halon
authors.affiliation: Department of Statistics, Wroclaw University of Economics, 53-345 Wroclaw, Poland.
authors.forename: Cyprian
authors.initials: C
authors.lastname: Kozyra
authors.affiliation: Medical Research Institute of Mongolia, 210526 Ulan Bator, Mongolia.
authors.forename: Tserenchunt
authors.initials: T
authors.lastname: Gansukh
authors.affiliation: Institute of Pathology, Charité Universitätsmedizin, D-10117 Berlin, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Lage
authors.affiliation: Department of Histology and Embryology, Wroclaw Medical University, 50-556 Wroclaw, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Surowiak
authors.affiliation: Department of Oncology and Division of Surgical Oncology, Wroclaw Medical University, 50-556 Wroclaw, Poland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Matkowski
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis / Q000096:biosynthesis*; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D014408:Biomarkers, Tumor; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases