Immunohistochemical expression of BRCA2 protein and allelic loss at the BRCA2 locus in prostate cancer. CRC/BPG UK Familial Prostate Cancer Study Collaborators.
Many epidemiological studies have reported an association between breast and prostate cancer. BRCA2 functions as a tumour-suppressor gene in about 35% of large familial breast-cancer clusters; its role in the pathogenesis of sporadic breast cancer is less clear. We have evaluated immunohistochemical expression of BRCA2 protein and allelic loss of markers at the BRCA2 locus in tissue derived both from sporadic and from familial cases of prostate cancer. Immunohistochemical analysis was performed in 167 paraffin-embedded archival specimens. Normal prostate and 75% (120/160) of prostate-cancer tissue did not express BRCA2 protein. However, 25% (40/160) of cancer cases did express patchy staining; of these, 17% (2711 60) expressed positive nuclear staining in normal glandular tissue adjacent to tumour (either in addition to, or, independent of tumour). Allelic loss is the hallmark of a tumour-suppressor gene. Markers flanking (D13S267, D13S260) and within (D13S171) the BRCA2 gene indicated allelic loss in at least one locus in 23% (17/73) of tumours analyzed. There was no difference in the rates of allelic loss between sporadic and familial tumours, nor was there any association between immunohistochemical staining and allelic loss. Although immunohistochemical staining provided no useful prognostic information, allelic loss at BRCA2 was shown in univariate analysis to be associated with poorer survival (log-rank test, p = 0.046).
CRC Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.
S M
SM
Edwards
W D
WD
Dunsmuir
C E
CE
Gillett
S R
SR
Lakhani
C
C
Corbishley
M
M
Young
R S
RS
Kirby
D P
DP
Dearnaley
A
A
Dowe
A
A
Ardern-Jones
J
J
Kelly
N
N
Spurr
D M
DM
Barnes
R A
RA
Eeles
D024682:BRCA2 Protein; D017353:Gene Deletion; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000235:genetics; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics
D024682:BRCA2 Protein; D005819:Genetic Markers; D009363:Neoplasm Proteins; D014157:Transcription Factors