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Nuclear-cytoplasmic PARP-1 expression as an unfavorable prognostic marker in lymph nodenegative early breast cancer: 15-year follow-up

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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.
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Document Type: Research Article

Affiliations: 1: Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, 50-556 Wroclaw, Poland 2: Laboratory of Mammotomic Biopsy, 4th Military Hospital, 50-001 Wroclaw, Poland 3: Department of Statistics, Wroclaw University of Economics, 53-345 Wroclaw, Poland 4: Medical Research Institute of Mongolia, 210526 Ulan Bator, Mongolia 5: Institute of Pathology, Charité Universitätsmedizin, D-10117 Berlin, Germany 6: Department of Histology and Embryology, Wroclaw Medical University, 50-556 Wroclaw, Poland 7: Department of Oncology and Division of Surgical Oncology, Wroclaw Medical University, 50-556 Wroclaw, Poland

Publication date: January 1, 2014

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