Allelic Losses in Localized Prostate Cancer: Association With Prognostic Factors

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Abstract
Loss of heterozygosity (LOH) is the most consistent genetic alteration in prostate cancer (CaP), frequently associated with advanced cancer and metastasis. We performed LOH analysis on 6 chromosomal regions of interest in localized CaP to obtain an overview of allelic losses in organ confined tumors and test the association with the usual prognostic factors. Tumoral and normal DNA were extracted from 48 radical prostatectomy specimens (all organ confined) with a Gleason score of 5 to 7. Biological and pathological data, such as prostate specific antigen (PSA), Gleason score and perineural invasion (PNI), were correlated with allelic losses at 7q31, 8p22, 12p13, 13q14, 16q23.2 and 18q21. Analysis was done by genotyping using highly informative microsatellites markers. The rate of LOH was 25% for chromosomes 13 and 18, and between 40% and 47% for chromosomes 7, 8, 12 and 16. The mean frequency of overall LOH events was less than 34%. Except for the 12p13 and 16q23.2 loci no significant correlation was found between LOH and PSA or Gleason score. PNI was significantly associated with LOH on 8p22 (p = 0.003) and with a high frequency of LOH events (greater than 34%) (p = 0.02). The frequency of allelic losses in localized and differentiated CaP is associated with PNI but not with the usual prognostic markers, such as PSA and Gleason score. The relationship between LOH on 8p22 and PNI suggests the presence on this region of a gene involved in epithelium/nerve interaction.