Fromont Gaëlle, Joulin Vincent, Chantrel-Groussard Karine, Vallancien Guy, Guillonneau Bertrand, Validire Pierre, Latil Alain, Cussenot Olivier
CeRePP, EA 3104, Universite Paris VII, France.
J Urol. 2003 Oct;170(4 Pt 1):1394-7. doi: 10.1097/01.ju.0000083329.89215.91.
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.
杂合性缺失（LOH）是前列腺癌（CaP）中最常见的基因改变，常与晚期癌症及转移相关。我们对局限性CaP的6个感兴趣染色体区域进行了LOH分析，以全面了解器官局限性肿瘤中的等位基因缺失情况，并检验其与常见预后因素的相关性。
从48例根治性前列腺切除术标本（均为器官局限性）中提取肿瘤及正常DNA，这些标本的 Gleason评分在5至7分之间。将生物学和病理学数据，如前列腺特异性抗原（PSA）、Gleason评分及神经周围浸润（PNI），与7q31、8p22、12p13、13q14、16q23.2和18q21处的等位基因缺失情况进行关联分析。采用高信息含量的微卫星标记进行基因分型分析。
13号和18号染色体的LOH率为25%，7号、8号、12号和16号染色体的LOH率在40%至47%之间。总体LOH事件的平均频率低于34%。除12p13和16q23.2位点外，未发现LOH与PSA或Gleason评分之间存在显著相关性。PNI与8p22处的LOH显著相关（p = 0.003），且与高频率的LOH事件（大于34%）相关（p = 0.02）。
局限性和分化型CaP中等位基因缺失的频率与PNI相关，但与常见的预后标志物如PSA和Gleason评分无关。8p22处的LOH与PNI之间的关系表明该区域存在一个参与上皮/神经相互作用的基因。
