Identification of genetic markers for prostatic cancer progression

Despite the high incidence of prostate cancer, only limited data are availa ble on genes or chromosomes specifically involved in its initiation and pro gression. We have applied comparative genomic hybridization to routinely pr ocessed, paraffin-embedded, tissues at different times in prostatic tumor p rogression to screen the tumor genome for gains and losses. Our panel inclu ded specimens derived from 56 different patients: 23 patients with primary, prostate-confined carcinomas; 18 patients with regional lymph node metasta ses; and 15 patients with distant metastases. Chromosome arms that most fre quently showed losses, included 13q (55%), 8p (48%), 6q (43%), 5q (32%), 16 q (25%), 18q (20%), 2q (18%), 4q (18%), 10q (18%), and Y (16%). Gains were often seen of chromosome arms 8q (36%), 17q (23%), Xq (23%), 7q (21%), 3q ( 18%), 9q (18%), 1q (16%), Xp (16%). Furthermore, specific high-level amplif ications, eg, of 1q21, 1q25, and Xq12 to q13, were found in metastatic canc ers. A significant accumulation of genetic changes in distant metastases wa s observed, eg, loss of 10q (p = 0.03) and gain of 7q )p = 0.03) sequences. in addition, investigation of a potential biomarker identified in previous studies by our group, ie, extra copies of #7 and/or #8, revealed a high pr evalence of 7pq and/or 8q gain in the distant metastases (p = 0.02). Import antly, gains were observed more frequently in tumors derived from progresso rs after radical prostatectomy, than in nonprogressors (mean time of follow -up, 74 months). Specifically, gain of chromosome 7pq and/or 8q sequences a ppeared an accurate discriminator between the progressors and nonprogressor s. Multivariate analysis showed a significant correlation between progressi ve disease and the number of chromosomes with gains. This correlation also held true when stage (p = 0.007) or grade (p = 0.002) were taken into accou nt. Likewise, this applied for gain of chromosome 7pq and/or 8q sequences ( p = 0.03 and p = 0.005 for stage or grade, respectively). Additionally, an increase in the number of chromosomes with gains per case was related to a decrease in biochemical progression-free survival (P-trend <0.001). More sp ecifically, the gain of 7pq and/or 8q sequences markedly reduced the bioche mical progression-free survival (p < 0.001). In conclusion, this study has, firstly, documented the spectrum of chromosomal alterations in subsequent stages of prostate cancer, a number of which had not been described previou sly. It allowed us to identify chromosomal regions related to advanced tumo r stage, ie, loss of 10q24 and gain of 7q11.2 and/or 7q31 sequences. Second ly, gain of 7pq and/or 8q was identified as a potential genetic discriminat or between progressors and nonprogressors after radical surgery.