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早期前列腺癌患者经前列腺按摩获取的前列腺细胞中基因不稳定的临床相关性

Clinical relevance of genetic instability in prostatic cells obtained by prostatic massage in early prostate cancer.

作者信息

Thuret R, Chantrel-Groussard K, Azzouzi A-R, Villette J-M, Guimard S, Teillac P, Berthon P, Houlgatte A, Latil A, Cussenot O

机构信息

CeRePP-EA3104, University Paris 7, France.

出版信息

Br J Cancer. 2005 Jan 31;92(2):236-40. doi: 10.1038/sj.bjc.6602311.

Abstract

We investigated whether genetic lesions such as loss of heterozygosity (LOH) are detected in prostatic cells obtained by prostatic massage during early diagnosis of prostate cancer (CaP) and discussed their clinical relevance. Blood and first urine voided after prostatic massage were collected in 99 patients with total prostate-specific antigen (PSA) between 4 and 10 ng ml(-1), prior to prostate biopsies. Presence of prostatic cells was confirmed by quantitative RT-PCR analysis of PSA mRNA. Genomic DNA was analysed for LOH on six chromosomal regions. One or more allelic deletions were found in prostatic fluid from 57 patients analysed, of whom 33 (58%) had CaP. Sensitivity and specificity of LOH detection and PSA free to total ratio <15% for positive biopsy were respectively 86.7 and 44% (P=0.002) for LOH, and 55 and 74% (P=0.006) for PSA ratio <15%. Analysis of LOH obtained from prostatic tumours revealed similar patterns compared to prostatic fluid cells in 86% of cases, confirming its accuracy. The presence of LOH of urinary prostatic cells obtained after prostatic massage is significantly associated with CaP on biopsy and may potentially help to identify a set of patients who are candidates for further prostate biopsies.

摘要

我们研究了在前列腺癌(CaP)早期诊断过程中,通过前列腺按摩获取的前列腺细胞中是否能检测到杂合性缺失(LOH)等基因损伤,并讨论了它们的临床相关性。在99例总前列腺特异性抗原(PSA)在4至10 ng/ml(-1)之间的患者进行前列腺活检之前,收集了前列腺按摩后的血液和首次排尿尿液。通过对PSA mRNA进行定量RT-PCR分析来确认前列腺细胞的存在。对六个染色体区域的基因组DNA进行了LOH分析。在分析的57例患者的前列腺液中发现了一个或多个等位基因缺失,其中33例(58%)患有CaP。活检阳性时,LOH检测的敏感性和特异性以及游离PSA与总PSA比值<15%,LOH分别为86.7%和44%(P=0.002),PSA比值<15%分别为55%和74%(P=0.006)。对前列腺肿瘤中获得LOH的分析显示,86%的病例与前列腺液细胞的模式相似,证实了其准确性。前列腺按摩后获得的尿前列腺细胞中LOH的存在与活检时的CaP显著相关,可能有助于识别一组适合进一步进行前列腺活检的患者。

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