Oxidative stress and counteracting mechanisms in hormone receptor positive, triple-negative and basal-like breast carcinomas
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- 作者：Peeter Karihtala (1)
Saila Kauppila (2)
Ylermi Soini (3)
? Arja-Jukkola-Vuorinen (1) - 刊名：BMC Cancer
- 出版年：2011
- 出版时间：December 2011
- 年：2011
- 卷：11
- 期：1
- 全文大小：225KB
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29. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/11/262/prepub - 作者单位：Peeter Karihtala (1)
Saila Kauppila (2)
Ylermi Soini (3)
? Arja-Jukkola-Vuorinen (1)
1. Department of Oncology and Radiotherapy, Oulu University Hospital and University of Oulu, Oulu, Finland
2. Department of Pathology, Oulu University Hospital and University of Oulu, Oulu, Finland
3. Department of Pathology, Oulu University Hospital and Department of Clinical Pathology and Forensic Medicine, Institute of Clinical Medicine, School of Medicine, Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland - ISSN：1471-2407
文摘
Background Triple-negative breast cancer (TNBC) and basal-like breast cancer (BLBC) are breast cancer subtypes with an especially poor prognosis. 8-Hydroxydeoxyguanosine (8-OHdG) is a widely used marker of oxidative stress and the redox-state-regulating enzymes peroxiredoxins (PRDXs) are efficient at depressing excessive reactive oxygen species. NF-E2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) are redox-sensitive transcription factors that regulate PRDX expression. This is the first study to assess oxidative stress and or cell redox state-regulating enzymes in TNBC and BLBC. Methods We assessed immunohistochemical expression of 8-OHdG, Nrf2, Keap1, PRDX III and PRDX IV in 79 women with invasive ductal breast carcinomas. Of these tumors, 37 represented TNBC (grade II-III tumors with total lack of ER, PR and human epidermal growth factor receptor 2 [HER2] expression). Control cases (n = 42) were ER-positive, PR-positive and HER2-negative. Of the 37 TNBCs, 31 had BLBC phenotype (TNBC with expression of cytokeratin 5/6 or epidermal growth factor receptor 1). Results Patients with TNBC had worse breast cancer-specific survival (BCSS) than the control group (p = 0.015). Expression of 8-OHdG was significantly lower in TNBC than in the non-TNBC group (p < 0.005). 8-OHdG immunostaining was associated with better BCSS (p = 0.01), small tumor size (p < 0.0001) and low grade (p < 0.0005). Keap1 overexpression was observed in the TNBC cohort (p = 0.001) and Keap1-positive patients had worse BCSS than Keap1-negative women (p = 0.014). PRDX IV was overexpressed in the TNBC vs. the non-TNBC group (p = 0.022). Conclusions Cellular redox state markers may be promising targets when elucidating the pathogenesis of TNBC.