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Counting alleles in single lesions of prostate tumors from ethnically diverse patients.

机译:计数来自不同种族患者的前列腺肿瘤单个病变中的等位基因。

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BACKGROUND: The presence of racial disparities in incidence and mortality rates are well-documented for prostate cancer. Nevertheless, it is unclear whether such disparities are due to genetic alterations that are involved in prostate cancer initiation. Here, we evaluated chromosome 8p allelic loss in a racially diverse cohort. METHODS: Laser-capture microdissection was used to isolate tumors cells from individual lesions in 153 prostate cancer patients, and 8p allelic status was determined by "counting alleles." Statistical analyses examined the association between pathologic predictors and biochemical recurrence. RESULTS AND CONCLUSIONS: Thirty percent of prostate lesions were missing an 8p allele at tumor initiation, while 51% of lesions lost an 8p allele during tumor progression. Biochemical recurrence after radical prostatectomy could be reliably predicted by surgical margin status only in lesions with extensive 8p allelic loss. There was, however, no racial disparity in 8p allelic loss at tumor initiation or during tumor progression, suggesting that the molecular event involved was similar between Caucasians and Africa Americans (CA and AA). Nonetheless, racial differences were present in values of prognostic factors for recurrence. Gleason score was the most important predictor of recurrence (HR=3.1, 95% CI=1.1, 9.2) in AA, while among CA, pathologic stage (HR=3.3, 95% CI=1.5, 7.6) and surgical margin (HR=4.7, 95% CI=1.8, 12.6) were the most important. Therefore, racial disparity in prostate cancer may be due to other factors that are involved in prostate cancer development.
机译:背景:前列腺癌的发病率和死亡率存在种族差异。然而,尚不清楚这种差异是否归因于前列腺癌起始过程中涉及的遗传改变。在这里,我们评估了一个种族多样化的队列中的8p染色体等位基因缺失。方法:采用激光捕获显微切割技术从153名前列腺癌患者的单个病变中分离出肿瘤细胞,并通过“计数等位基因”确定8p等位基因状态。统计分析检查了病理预测因素和生化复发之间的关联。结果与结论:30%的前列腺病变在肿瘤发生时缺失了8p等位基因,而51%的病变在肿瘤进展过程中缺失了8p等位基因。仅在具有广泛的8p等位基因缺失的病变中,通过手术切缘状态才能可靠地预测根治性前列腺切除术后的生化复发。但是,在肿瘤发生时或肿瘤进展过程中8p等位基因的丢失没有种族差异,这表明高加索人和非裔美国人(CA和AA)所涉及的分子事件相似。然而,种族差异存在于复发的预后因素的价值。格里森评分是AA复发的最重要预测指标(HR = 3.1,95%CI = 1.1,9.2),而在CA中,病理分期(HR = 3.3,95%CI = 1.5,7.6)和手术切缘(HR = 4.7、95%CI = 1.8、12.6)是最重要的。因此,前列腺癌的种族差异可能是由于前列腺癌发展中涉及的其他因素造成的。

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