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Intracellular location of brca2 protein expression and prostate cancer progression in the swedish watchful waiting cohort

Thorgeirsson, Tryggvi
Jordahl, Kristina M.
Flavin, Richard
Epstein, Mara Meyer
Fiorentino, Michelangelo
Andersson, Swen-Olof
Andren, Ove
Rider, Jennifer R.
Mosquera, Juan Miguel
Ingoldsby, Helen
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Publication Date
2016-01-16
Type
Article
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Citation
Thorgeirsson, Tryggvi; Jordahl, Kristina M. Flavin, Richard; Epstein, Mara Meyer; Fiorentino, Michelangelo; Andersson, Swen-Olof; Andren, Ove; Rider, Jennifer R.; Mosquera, Juan Miguel; Ingoldsby, Helen; Fall, Katja; Tryggvadottir, Laufey; Mucci, Lorelei A.; , (2016). Intracellular location of brca2 protein expression and prostate cancer progression in the swedish watchful waiting cohort. Carcinogenesis 37 (3), 262-268
Abstract
We found association between prognosis of prostate cancer patients and positive staining for the BRCA2 protein in diagnostic cancer tissue. Positive staining at the cell membrane was associated with improved survival whereas staining in the cytoplasm predicted adverse outcome.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.
Funder
Publisher
Oxford University Press (OUP)
Publisher DOI
10.1093/carcin/bgw001
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland