Overexpression of RAD51 occurs in aggressive prostatic cancer.
OBJECTIVE
To test the hypothesis that, in a matched series of prostatic cancers, either with or without BRCA1 or BRCA2 mutations, RAD51 protein expression is enhanced in association with BRCA mutation genotypes.


RESULTS
RAD51 expression identified immunohistochemically was compared between prostatic cancers occurring in BRCA1 or BRCA2 mutation carriers and controls. RAD51 protein expression in the cytoplasm and nuclei of the benign tissues was significantly less than in the malignant tissues (P < 0.001). In all cancers, cytoplasmic expression of RAD51 was more prevalent and associated with higher Gleason score (P < 0.05) irrespective of BRCA mutational status, than its expression in benign tissues (P < 0.001). Although nuclear immunoreactivity was not observed in BRCA-associated cancers with Gleason score < or =7, it was significantly increased in all other groups of prostatic cancers when compared with benign tissues (P < 0.001).


CONCLUSIONS
RAD51 protein is strongly expressed in high-grade prostatic cancers, whether sporadic or associated with BRCA germ-line mutations. Distinct localization of RAD51 between cytoplasm and nucleus, particularly in cancers of Gleason score < or =7, reflects distinct levels of RAD51 regulatory activity, from transcription to DNA repair. This biomarker may be of value in identifying patients requiring urgent treatment at diagnosis as well as in analysing biological mechanisms underlying aggressive phenotype of human prostatic cancer.
Mitra
Anita
A
Translational Cancer Genetics Team, Section of Cancer Genetics, The Institute of Cancer Research, Sutton, Surrey, UK.
Jameson
Charles
C
Barbachano
Yolanda
Y
Sanchez
Lydia
L
Kote-Jarai
Zsofia
Z
Peock
Susan
S
Sodha
Nayanta
N
Bancroft
Elizabeth
E
Fletcher
Anne
A
Cooper
Colin
C
Easton
Douglas
D
Eeles
Rosalind
R
Foster
Christopher S
CS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D002452:Cell Count; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D051135:Rad51 Recombinase / Q000378:metabolism*; D012720:Severity of Illness Index
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C495153:RAD51 protein, human; D051135:Rad51 Recombinase