Dolan Kevin, Morris Anthony I, Gosney John R, Field John K, Sutton Robert
University of Liverpool and Department of Surgery, Royal Liverpool University Hospital, Liverpool, UK.
J Gastroenterol Hepatol. 2003 Jun;18(6):683-9. doi: 10.1046/j.1440-1746.2003.03048.x.
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.
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.
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).
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.
对巴雷特食管患者进行腺癌的内镜监测成本高昂，每48 - 441患者年的随访中才能检测到1例癌症。在恶性和癌前巴雷特食管中已检测到基因异常，包括肿瘤抑制基因位点的杂合性缺失。这项前瞻性研究的目的是确定杂合性缺失分析是否能识别出腺癌风险最高的巴雷特食管患者，这些患者最适合进行内镜监测。
作为巴雷特监测项目的一部分，对48例患者的内镜活检组织进行杂合性缺失分析，使用14个微卫星标记，这些标记先前已被证明能在超过30%的食管腺癌中检测到杂合性缺失。患者接受了中位时间为5年的内镜随访。
在9例患者中检测到杂合性缺失。3例5号染色体长臂或9号染色体短臂杂合性缺失的患者未进展至化生以上阶段。在6例患者中检测到17号染色体短臂11.1 - 13区域的杂合性缺失，所有这些患者在随访期间均出现发育异常和/或癌症（4例低级别发育异常，1例高级别发育异常和1例腺癌）。
17号染色体短臂11.1 - 13区域的杂合性缺失可识别有肿瘤进展风险的巴雷特食管患者，并可在监测期间确定内镜检查频率时补充组织学检查。
