title: High frequency of allelic losses in high-grade prostate cancer is associated with biochemical progression after radical prostatectomy.
abstract: Loss of heterozygosity (LOH) is the most consistent genetic change in prostate cancer (CaP). We aimed, to correlate specific LOH and the overall LOH frequency, to disease progression after radical prostatectomy (RP) in high-grade CaP. Between January 1990 through December 1998, 126 patients who underwent RP (cT1-T2), Gleason 8-10, were pT3, or pN1, or SM(+) (surgical margins). Nine were lost of follow-up, 39/117 (33%) had no biochemical progression (mean follow-up: 45 months). After exclusion for preoperative PSA >50 ng/mL, a case-control study was designed by matching 26 of these cases with 26 similar patients without biochemical progression (criteria: pT, pN, year of surgery). Using microsatellite markers, LOH were assessed on six chromosomal regions (7q31, 8p22, 12p13, 13q14, 16q23.2, 18q21). No prognostic value was associated with LOH at any one specific locus. However, the overall LOH frequency (five classes, cutoff of 60%), was significantly higher if progression (P = 0.02; P = 0.03) in SM(+) patients, and was near statistical significance (P = 0.08; P = 0.07) for the overall case-control population. In multivariate analysis (overall population), the overall LOH rate > or =60% was independently associated with progression [P = 0.035; Odds Ratio (OR) = 5.54]. An overall LOH rate > or =60% predicted poor outcome in 85% of SM(+) patients and 69% of the whole population. Our results suggest that the overall rate of LOH at chromosomal "hot spots" is more likely to be predictive of recurrence than the presence of LOH at any one particular locus. Moreover, the identification of a threshold of LOH could help in predicting patients with poor outcome who may be candidates for local or systemic adjuvant therapies.
authors.affiliation: Department of Urology, Detroit Medical Center and Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA. Antoine.Valeri@univ-brest.fr
authors.forename: Antoine
authors.initials: A
authors.lastname: Valeri
authors.forename: Gaelle
authors.initials: G
authors.lastname: Fromont
authors.forename: Wael
authors.initials: W
authors.lastname: Sakr
authors.forename: Rahmène
authors.initials: R
authors.lastname: Azzouzi
authors.forename: Jyotirmoy
authors.initials: J
authors.lastname: Dey
authors.forename: Karine
authors.initials: K
authors.lastname: Chantrel-Groussard
authors.forename: Alain
authors.initials: A
authors.lastname: Latil
authors.forename: Philippe
authors.initials: P
authors.lastname: Berthon
authors.forename: Olivier
authors.initials: O
authors.lastname: Cussenot
authors.forename: J Edson
authors.initials: JE
authors.lastname: Pontes
authors.forename: Michael L
authors.initials: ML
authors.lastname: Cher
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D018450:Disease Progression; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D016896:Treatment Outcome
chemical_list: D017430:Prostate-Specific Antigen