Tumor protein expression of the DNA repair gene BRCA1 and lethal prostate cancer.
Adult
Aged
BRCA1 Protein
/ genetics
Biomarkers, Tumor
DNA Repair
/ genetics
Disease Progression
Follow-Up Studies
Gene Expression Regulation, Neoplastic
/ genetics
Humans
Male
Middle Aged
Mutation
/ genetics
Neoplasm Grading
Neoplasm Metastasis
Neoplasm Proteins
/ genetics
Neoplasms, Bone Tissue
/ genetics
Prostatic Neoplasms
/ genetics
Journal
Carcinogenesis
ISSN: 1460-2180
Titre abrégé: Carcinogenesis
Pays: England
ID NLM: 8008055
Informations de publication
Date de publication:
14 07 2020
14 07 2020
Historique:
received:
16
03
2020
revised:
26
05
2020
accepted:
11
06
2020
pubmed:
20
6
2020
medline:
7
2
2021
entrez:
20
6
2020
Statut:
ppublish
Résumé
DNA repair genes are commonly altered in metastatic prostate cancer, but BRCA1 mutations are rare. Preliminary studies suggest that higher tumor expression of the BRCA1 protein may be associated with worse prognosis. We undertook a prospective study among men with prostate cancer in the Health Professionals Follow-up Study and evaluated BRCA1 via immunohistochemical staining on tissue microarrays. BRCA1 was expressed in 60 of 589 tumors. Prevalence of BRCA1 positivity was 43% in the 14 men with metastases at diagnosis compared with 9% in non-metastatic tumors [difference, 33 percentage points; 95% confidence interval (CI), 7-59]. BRCA1-positive tumors had 2.16-fold higher Ki-67 proliferative indices (95% CI, 1.18-3.95), higher tumor aneuploidy as predicted from whole-transcriptome profiling, and higher Gleason scores. Among the 575 patients with non-metastatic disease at diagnosis, we evaluated the association between BRCA1 expression and development of lethal disease (metastasis or cancer-specific death, 69 events) during long-term follow-up (median, 18.3 years). A potential weak association of BRCA1 positivity with lethal disease (hazard ratio, 1.61; 95% CI, 0.82-3.15) was attenuated when adjusting for age, Gleason score and clinical stage (hazard ratio, 1.11; 95% CI, 0.54-2.29). In summary, BRCA1 protein expression is a feature of more proliferative and more aneuploid prostate tumors and is more common in metastatic disease. While not well suited as a prognostic biomarker in primary prostate cancer, BRCA1 protein expression may be most relevant in advanced disease.
Identifiants
pubmed: 32556091
pii: 5859098
doi: 10.1093/carcin/bgaa061
pmc: PMC7359768
doi:
Substances chimiques
BRCA1 Protein
0
BRCA1 protein, human
0
Biomarkers, Tumor
0
Neoplasm Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
904-908Subventions
Organisme : NCI NIH HHS
ID : P50 CA090381
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA167552
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA228696
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA113913
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA136578
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006516
Pays : United States
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Références
Cell. 2002 Jan 25;108(2):171-82
pubmed: 11832208
J Clin Oncol. 2019 Feb 20;37(6):490-503
pubmed: 30625039
Nat Med. 2018 May;24(5):628-637
pubmed: 29713086
Proc Natl Acad Sci U S A. 2019 Jun 4;116(23):11428-11436
pubmed: 31061129
J Natl Cancer Inst. 2014 Feb;106(2):djt430
pubmed: 24463248
J Clin Oncol. 2009 Jul 20;27(21):3459-64
pubmed: 19433685
Cancer Res. 2010 Apr 15;70(8):3136-9
pubmed: 20388772
Science. 2008 Mar 7;319(5868):1352-5
pubmed: 18323444
Lancet Oncol. 2020 Jan;21(1):162-174
pubmed: 31806540
N Engl J Med. 2020 May 28;382(22):2091-2102
pubmed: 32343890
N Engl J Med. 2015 Oct 29;373(18):1697-708
pubmed: 26510020
Eur Urol. 2015 Aug;68(2):186-93
pubmed: 25454609
N Engl J Med. 2016 Aug 4;375(5):443-53
pubmed: 27433846
Mol Cancer. 2009 Jul 14;8:48
pubmed: 19602291
Int J Cancer. 2009 Feb 15;124(4):806-15
pubmed: 19035454
Eur Urol. 2017 May;71(5):740-747
pubmed: 27989354
Cancer Res. 2003 Oct 1;63(19):6221-8
pubmed: 14559807
J Pathol. 2003 Jun;200(2):207-13
pubmed: 12754741
Am J Hum Genet. 1995 Jan;56(1):265-71
pubmed: 7825587
Cell. 2006 Nov 3;127(3):539-52
pubmed: 17081976
Am J Epidemiol. 2005 Aug 1;162(3):199-200
pubmed: 15987728
Nat Genet. 1994 Dec;8(4):399-404
pubmed: 7894493
Science. 2017 Mar 17;355(6330):1152-1158
pubmed: 28302823
Cancer Epidemiol Biomarkers Prev. 2012 Sep;21(9):1497-509
pubmed: 22736790
Lancet. 1994 Mar 19;343(8899):692-5
pubmed: 7907678
Int J Cancer. 2019 Feb 1;144(3):607-614
pubmed: 30265376
Carcinogenesis. 2015 Jun;36(6):639-47
pubmed: 25863129
Proc Natl Acad Sci U S A. 2020 Jan 28;117(4):2084-2091
pubmed: 31932421
Proc Natl Acad Sci U S A. 2019 Jun 4;116(23):11390-11395
pubmed: 31085648
Clin Cancer Res. 2010 Apr 1;16(7):2115-21
pubmed: 20215531
Ann Oncol. 2011 Nov;22(11):2403-10
pubmed: 21368065
Nature. 2006 Nov 30;444(7119):633-7
pubmed: 17136093
Br J Cancer. 2012 May 8;106(10):1697-701
pubmed: 22516946
Int J Gynecol Cancer. 2006 Jan-Feb;16 Suppl 1:166-71
pubmed: 16515585
Clin Cancer Res. 2009 Mar 1;15(5):1558-65
pubmed: 19223505