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Carcinogenesis. 2016 Mar;37(3):262-8. doi: 10.1093/carcin/bgw001. Epub 2016 Jan 16.

Intracellular location of BRCA2 protein expression and prostate cancer progression in the Swedish Watchful Waiting Cohort.

Author information

1
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA, Public Health Sciences, University of Iceland, 101 Reykjavik, Iceland.
2
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
3
Center for Molecular Oncologic Pathology, Dana Farber Cancer Institute, Boston, MA 02215, USA, Department of Histopathology, St. James's Hospital Dublin, Dublin 8, Ireland, Trinity College Dublin, Dublin, Ireland.
4
Department of Medicine and the Meyers Primary Care Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
5
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA, "F. Addarii" Institute of Oncology and Transplantation Pathology, S.Orsola-Malpighi Hospital, Bologna University, 40126 Bologna, Italy.
6
Department of Urology, Faculty of Medicine and Health, Örebro University, SE 701 82 Örebro, Sweden.
7
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA, Institute for Precision Medicine of Weill Cornell Medical College and New York Presbyterian, New York, NY 10065, USA.
8
National University of Ireland, Shantalla Road, Galway, Ireland.
9
Clinical Epidemiology and Biostatistics, Faculty of Medicine and Health, Örebro University, SE 701 82 Örebro, Sweden.
10
Icelandic Cancer Registry, 105 Reykjavik, Iceland and Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland laufeyt@krabb.is.

Abstract

Prostate cancer patients with inherited BRCA2 mutations have a survival disadvantage. However, it is unknown whether progression is associated with BRCA2 protein expression in diagnostic prostate cancer tissue, among men without inherited mutations. We conducted a nested case-control study within the Swedish Watchful Waiting cohort. The case group included all 71 patients who died from prostate cancer within 5 years from diagnosis and controls were all patients (n = 165) who lived at least 7 years after diagnosis. Tissue microarrays were stained using antibodies for C- and N-terminal domains of the BRCA2 protein. Location (nuclear, cytoplasmic and membranous) and magnitude (intensity and percentage) of expression were assessed. Logistic regression models produced odds ratios (OR) and 95% confidence intervals (CI) adjusted for age, year of diagnosis and Gleason score. Positive BRCA2 staining at the cell membrane was associated with reduced risk of death within 5 years (N-terminal: OR = 0.47, 95% CI = 0.21-1.04, P = 0.06; C-terminal: OR = 0.41, 95% CI = 0.18-0.91, P = 0.03) and low Gleason scores (P = 0.006). Positive cytoplasmic C-terminal staining was associated with higher Gleason scores and increased lethality (OR = 3.61, 95% CI = 1.61-8.07, P = 0.002). BRCA2 protein expression at the cell membrane and lack of C-terminal expression in the cytoplasm were associated with a reduced risk of rapidly fatal prostate cancer. BRCA2 protein expression in prostate cancer tissue may have independent prognostic value. The potential biological significance of BRCA2 expression at the cell membrane warrants further investigation.

PMID:
26775038
DOI:
10.1093/carcin/bgw001
[Indexed for MEDLINE]

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