Genetic evaluation of localized prostate cancer in a cohort of forty patients: gain of distal 8q discriminates between progressors and nonprogressors.
Over-representation of sequences on chromosome 7 and 8 have been reported to be associated with aggressive behavior of prostate cancer. In this study we have performed a molecular cytogenetic survey by comparative genomic hybridization of a cohort of 40 prostate cancer patients, consisting of 20 progressors and 20 nonprogressors, after radical surgery for localized adenocarcinoma. Progression was defined as a biochemical relapse, ie, an elevation in prostate-specific antigen level in the serum. The mean follow-up after prostatectomy for the progressor group was 10.6 years, for the nonprogressor group, 9.1 years. Using comparative genomic hybridization, we found that progressors harbored on average more aberrations than nonprogressors. Gains were especially more prominent among progressors (p < 0.05), whereas a statistical trend was detected for losses (p = 0.10). As a consequence we examined all chromosome arms separately. The frequencies of loss for areas known to be frequently deleted in prostate cancer, such as 6q, 8p, or 13q, were not different between the two groups. A tendency was observed for more frequent gain on 3q in the progressor group (p = 0.09). However, gain of 8q (minimal overlapping region at 8q24-qter) was significantly more frequent in the progressor group (p = 0.04). This biomarker retained its significance when adjusted for the factors age, tumor grade, tumor stage, resection margin status, and preoperative prostate-specific antigen level. In conclusion we have created a map of genetic changes in progressive and nonprogressive prostatic carcinomas. Importantly, the presence of gain of distal 8q markedly reduced the progression-free survival, suggesting a clinical role for 8q gain in assessing the malignant potential of localized prostatic adenocarcinoma.
van Dekken
Herman
H
Department of Pathology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, the Netherlands. vandekken@path.fgg.eur.nl
Alers
Janneke C
JC
Damen
Irma A A J
IA
Vissers
Kees J
KJ
Krijtenburg
Pieter-Jaap
PJ
Hoedemaeker
Robert F
RF
Wildhagen
Mark F
MF
Hop
Wim C J
WC
van der Kwast
Theodorus H
TH
Tanke
Hans J
HJ
Schröder
Fritz H
FH
D000368:Aged; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7; D002898:Chromosomes, Human, Pair 8; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D018450:Disease Progression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*
D004273:DNA, Neoplasm; D017430:Prostate-Specific Antigen