title: Immunohistochemical expression of BRCA1 and lethal prostate cancer.
abstract: BRCA1 functions as a tumor suppressor; recent work suggests that BRCA1 may also induce cell cycle arrest to allow for DNA repair. We hypothesized that BRCA1 expression in prostate tumor tissue may be associated with prostate cancer progression through regulation of the cell cycle. We used immunohistochemistry to evaluate BRCA1 protein expression in archival tumor samples from 393 prostate cancer cases in the Physicians' Health Study. The men were followed prospectively from diagnosis to development of metastases and mortality. Fifteen percent of tumors stained positive for BRCA1. BRCA1-positive tumors had substantially increased tumor proliferation index compared with negative tumors (47.0 Ki67-positive nuclei versus 10.3, P = 0.0016) and were more likely to develop lethal cancer compared with BRCA1-negative tumors (hazard ratio, 4.6; 95% confidence interval, 2.4-8.7). These findings strengthen the hypothesis that BRCA1 plays a role in cell cycle control and show that BRCA1 is a marker of clinical prostate cancer prognosis. Cancer Res; 70(8); 3136-9. (c)2010 AACR.
authors.affiliation: Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. michelangelo_fiorentino@dfci.harvard.edu
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Fiorentino
authors.forename: Gregory
authors.initials: G
authors.lastname: Judson
authors.forename: Kathryn
authors.initials: K
authors.lastname: Penney
authors.forename: Richard
authors.initials: R
authors.lastname: Flavin
authors.forename: Jennifer
authors.initials: J
authors.lastname: Stark
authors.forename: Christopher
authors.initials: C
authors.lastname: Fiore
authors.forename: Katja
authors.initials: K
authors.lastname: Fall
authors.forename: Neil
authors.initials: N
authors.lastname: Martin
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sinnott
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
authors.forename: Meir
authors.initials: M
authors.lastname: Stampfer
authors.forename: Howard D
authors.initials: HD
authors.lastname: Sesso
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
authors.forename: Stephen
authors.initials: S
authors.lastname: Finn
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.forename: Lorelei
authors.initials: L
authors.lastname: Mucci
mesh_terms: D000368:Aged; D019313:BRCA1 Protein / Q000096:biosynthesis* / Q000235:genetics*; D014408:Biomarkers, Tumor; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D009154:Mutation; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen
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