Genomic markers for prostate cancer progression: assessment of the malignant potential of localized prostatic adenocarcinomas
01 / 2002 - 01 / 2006
Website Nederlandse Kankerbestrijding
Prostate cancer is now the most commonly diagnosed cancer in males in Western countries with a high socio-economic standard, and its mortality is only surpassed by that of lung cancer. Despite this high prevalence no objective (cyto)genetic or histopathologic parameters have been found so far that can predict the biological behaviour of prostatic cancers. In this respect the choice of treatment of, especially, (small) localized carcinomas is difficult. Contrastingly, due to surveillance and screening programs, localized stages of prostatic cancer are encountered more frequently. We reported that chromosomal gains, defined by comparative genomic hybridization (CGH) were more frequent in tumors derived from progressors after radical prostatectomy, than in non-progressors. Specifically, gain of chromosome 7pq and/or 8q sequences appeared an accurate discriminator between the progressors and non-progressors, and was significantly related to progressive disease. Importantly, we found that these aberrations are also discriminated in a subgroup of early prostatic cancers, i.e. in small localized adenocarcinomas as detected by the Rotterdam screening program. The purpose of this investigation is to search for genetic prognosticators in prostate cancer focusing on chromosomes 7 and 8. These biomarkers will be used to assess tumor progression in localized forms of prostatic cancer. The project entails the evaluation of a unique, clinico-pathologically matched, series of localized adenocarcinomas from progressors and non-progressors after radical prostatectomy. The following stages are carried out: 1. Micro-array CGH screening of the matched cohort of prostatic carcinomas with custom-made high-density BAC-array DNA chips of chromosome 7 and 8. 2. Screening of candidate genes by genotypic analysis of tissue arrays of the cancer specimens of this cohort using DNA in situ hybridization. 3. Prospective evaluation of the selected biomarkers by DNA in situ hybridization of pairs of prostate cancer needle biopsies and radical prostatectomies. The described approach aims at the detection of new genetic parameters with prognostic implications for localized prostatic adenocarcinoma. These specific genetic aberrations can be assessed in needle biopsies of prostate cancer specimens. In cases concerning localized lesions our biomarkers would define criteria for active treatment as opposed to watchful waiting.