Allelic loss at 16q23.2 is associated with good prognosis in high grade prostate cancer

Abstract

Loss of heterozygosity (LOH) at 16q23.2 is an early and frequent event in prostate cancer. LOH is thought to be involved in tumor development and progression mainly through inactivation of tumor suppressor genes. However, it has been demonstrated that LOH at 16q23.2 is an independent marker of good prognosis in breast cancer. In the present study, we evaluated the clinical relevance of 16q23.2 LOH in prostate cancer, together with other LOH frequently associated with this disease. Tumoral and normal DNA were extracted from 61 radical prostatectomies, including 30 pT2 tumors with low Gleason score 5,6 (group 1), and 31 pT3 high grade (G8-9) tumors (group 2). Median follow-up after surgery was 42 months. Three patients reccured in group 1, and 20 in group 2. LOH analysis was performed using highly informative microsatellites markers, at 16q23.2, and at other chromosome loci frequently deleted in prostate cancer: 7q31, 8p22, 12p13, 13q14, and 18q21. LOH at 16q23.2 is associated with low stage low grade tumors and lower preoperative PSA, while LOH at 8p22 is more frequent in high stage high grade prostate cancer. In group 2, 16q23.2 LOH was the only predictor of disease-free survival in univariate and multivariate analysis, and the cumulative LOH rate was not higher in patients non-deleted for 16q23.2. These results emphasize the interest of 16q23.2 as an independent prognostic factor in high-grade prostate cancer, and suggest that this chromosomal region may contain a gene involved in tumor progression.