title: Elevated expression of Ki-67 identifies aggressive prostate cancers but does not distinguish BRCA1 or BRCA2 mutation carriers.
abstract: Prostate cancers in men with germline BRCA1 and BRCA2 mutations are more aggressive than morphologically similar cancers in men without these mutations. This study was performed to test the hypothesis that enhanced expression of Ki-67, as a surrogate of cell proliferation, is a characteristic feature of prostate cancers occurring in BRCA1 or BRCA2 mutation carriers. The study cohort comprised 20 cases of prostate cancer in mutation carriers and 126 control sporadic prostate cancers. Of the combined sample cohort, 65.7% stained only within malignant tissues while 0.7% stained in both malignant and benign tissues (p<0.001). Significantly increased expression of Ki-67 occurred in prostate cancers with higher Gleason score (p<0.001). Elevated Ki-67 expression was identified in 71% of prostate cancers in BRCA1 or BRCA2 mutation carriers and in 67% of the sporadic controls (p>0.5). Similar results were obtained when the data were analysed using a threshold set at 3.5 and 7.1%. This study shows that elevated expression of Ki-67 is associated both with aggressive prostate cancers and with high Gleason score irrespective of whether their occurrence is against a background of BRCA1 or BRCA2 mutations or as sporadic disease. The data suggest that, since elevated Ki-67 does not distinguish prostate cancers occurring in BRCA1 or BRCA2 mutation carriers from sporadic prostatic malignancies, the effects of these genetic mutations are probably independent. While all prostate cancers occurring in the presence of BRCA germline mutations are clinically aggressive, their potentially different phenotypes consistently involve maximal rates of cell proliferation.
authors.affiliation: Translational Cancer Genetics Team, The Institute of Cancer Research, Surrey, UK.
authors.forename: A V
authors.initials: AV
authors.lastname: Mitra
authors.forename: C
authors.initials: C
authors.lastname: Jameson
authors.forename: Y
authors.initials: Y
authors.lastname: Barbachano
authors.forename: N
authors.initials: N
authors.lastname: Sodha
authors.forename: Z
authors.initials: Z
authors.lastname: Kote-Jarai
authors.forename: A
authors.initials: A
authors.lastname: Javed
authors.forename: E
authors.initials: E
authors.lastname: Bancroft
authors.forename: A
authors.initials: A
authors.lastname: Fletcher
authors.forename: C
authors.initials: C
authors.lastname: Cooper
authors.forename: S
authors.initials: S
authors.lastname: Peock
authors.forename: D
authors.initials: D
authors.lastname: Easton
authors.forename: R
authors.initials: R
authors.lastname: Eeles
authors.forename: C S
authors.initials: CS
authors.lastname: Foster
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006580:Genetic Carrier Screening / Q000379:methods; D018095:Germ-Line Mutation; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen