Immunohistochemical expression of BRCA1 and lethal prostate cancer.
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.
Fiorentino
Michelangelo
M
Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. michelangelo_fiorentino@dfci.harvard.edu
Judson
Gregory
G
Penney
Kathryn
K
Flavin
Richard
R
Stark
Jennifer
J
Fiore
Christopher
C
Fall
Katja
K
Martin
Neil
N
Ma
Jing
J
Sinnott
Jennifer
J
Giovannucci
Edward
E
Stampfer
Meir
M
Sesso
Howard D
HD
Kantoff
Philip W
PW
Finn
Stephen
S
Loda
Massimo
M
Mucci
Lorelei
L
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*
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen
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