Loss of heterozygosity on chromosome 17p predicts neoplastic progression in Barrett's esophagus
Loss of heterozygosity on chromosome 17p predicts neoplastic progression in Barrett's esophagus
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DOI：
10.1046/j.1440-1746.2003.03048.x
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发表时间：
2003-06-01
影响因子：
4.1
通讯作者：
Sutton, R
中科院分区：
文献类型：
--
作者：
Dolan, K;Morris, AI;Sutton, R
背景和目的：Barrett‘s食管腺癌患者的内窥镜监测费用高昂，每48-441名患者随访一次就会发现一例。遗传异常，包括肿瘤抑制基因位点的杂合性丢失，已经在恶性和癌前巴雷特食道中被检测到。这项前瞻性研究的目的是确定杂合性丢失分析是否可以确定Barrett食管腺癌风险最高的患者，对他们来说，内窥镜检查是最合适的。方法：对48名患者的内窥镜活检进行杂合性丢失分析，作为Barrett监测计划的一部分，使用先前显示的14个微卫星标记来检测30%以上食管腺癌的杂合性丢失。患者在内窥镜下平均随访5年。结果：9例患者检测到杂合性丢失。3例5q或9p染色体杂合性缺失的患者没有进展到化生以上。在6例患者中检测到17p11.1-p13杂合性缺失，所有患者在随访期间均表现为不典型增生和/或癌(4例轻度不典型增生，1例高度不典型增生和1例腺癌)。结论：染色体17p上17p11.1-p13杂合性缺失可以识别Barrett‘s食管瘤进展的风险，并可以补充组织学在监测期间确定胃镜检查的频率。(C)2003年Blackwell出版亚洲私人有限公司。
Background and Aim: Endoscopic surveillance for adenocarcinoma in patients with Barrett's esophagus is costly, with one cancer detected every 48-441 patient years of follow up. Genetic abnormalities, including loss of heterozygosity at sites of tumor suppressor genes, have been detected in malignant and premalignant Barrett's esophagus. The aim of this prospective study was to determine if loss of heterozygosity analysis could identify patients with Barrett's esophagus at greatest risk of adenocarcinoma, for whom endoscopic surveillance is most appropriate.Methods: Loss of heterozygosity analysis was performed on endoscopic biopsies from 48 patients as part of a Barrett's surveillance program using 14 microsatellite markers shown previously to detect loss of heterozygosity in more than 30% of esophageal adenocarcinomas. Patients were followed up endoscopically for a median of 5 years.Results: Loss of heterozygosity was detected in nine patients. Three patients with loss of heterozygosity on chromosome 5q or 9p did not progress beyond metaplasia. Loss of heterozygosity at 17p11.1-p13 was detected in six patients, all of whom demonstrated dysplasia and/or carcinoma during follow up (four low-grade dysplasia, one high-grade dysplasia and one adenocarcinoma).Conclusion: Loss of heterozygosity at 17p11.1-p13 on chromosome 17p identifies patients with Barrett's esophagus at risk of neoplastic progression and can supplement histology in determining the frequency of endoscopy during surveillance. (C) 2003 Blackwell Publishing Asia Pty Ltd.