Marqueurs tissulaires phénotypiques et moléculaires associés à la progression du cancer prostatique

2005 
A better knowledge of both the mechanisms underlying prostate cancer progression and the factors predictive of evolution is a key issue for the management of patients follow-up and treatment. We first tried to improve the analysis of commonly used histopronostic factors. We evaluated the impact of the positive surgical margin size after prostatectomy, and showed that the margin size is predictive of the incidence of residual tumor, therefore representing an additional phenotypic marker for the risk of progression. We then analyzed potentiel prognostic factors among the genomic alterations and gene expression dysregulations associated with prostate cancer progression. The incidence of loss of heterozygosity (LOH) on 6 chromosomal regions of interest was determined in relation with histoprognostic factors and evolution. We observed that l)the overall rate of LOH increased with cancer progression, 2)LOH at 8p22 is specifiquely associated with perineural invasion, suggesting the presence on this region of a gene involved in epithelium/nerve interaction. At the end, 3)LOH at 16q23. 2 is associated with favorable histopronostic factors, and constitute an independant marker of good prognosis, suggesting that this chromosomal region may contain a gene involved in tumor progression. The expression of 300 genes was analyzed by quantitative RTPCR. We observed a differential gene expression between normal prostate tissue, prostate cancer, and benign proliferative disorders. A specific gene expression profile was also identified in advanced hormone-refractory cancers whe compared to localized tumors, which prompt to study the predictive and therapeutic value of these dysregulated gene.
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