title: Overexpression of RAD51 occurs in aggressive prostatic cancer.
abstract: 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.
authors.affiliation: Translational Cancer Genetics Team, Section of Cancer Genetics, The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Anita
authors.initials: A
authors.lastname: Mitra
authors.forename: Charles
authors.initials: C
authors.lastname: Jameson
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Barbachano
authors.forename: Lydia
authors.initials: L
authors.lastname: Sanchez
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Kote-Jarai
authors.forename: Susan
authors.initials: S
authors.lastname: Peock
authors.forename: Nayanta
authors.initials: N
authors.lastname: Sodha
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bancroft
authors.forename: Anne
authors.initials: A
authors.lastname: Fletcher
authors.forename: Colin
authors.initials: C
authors.lastname: Cooper
authors.forename: Douglas
authors.initials: D
authors.lastname: Easton
authors.forename: Rosalind
authors.initials: R
authors.lastname: Eeles
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Foster
mesh_terms: 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
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C495153:RAD51 protein, human; D051135:Rad51 Recombinase