利用蔗糖酶异麦芽糖酶和p53检测贲门巴雷特腺癌

Detection of Barrett's adenocarcinoma of the gastric cardia with sucrase isomaltase and p53.

作者信息

Iannettoni M D, Lee S S, Bonnell M R, Sell T L, Whyte R I, Orringer M B, Beer D G

机构信息

Department of Surgery, University of Michigan, Ann Arbor 48109-0344, USA.

出版信息

Ann Thorac Surg. 1996 Nov;62(5):1460-5; discussion 1465-6. doi: 10.1016/0003-4975(96)00749-7.

DOI:10.1016/0003-4975(96)00749-7

PMID:8893584

Abstract

BACKGROUND

Routine surveillance for dysplastic epithelium in patients with Barrett's esophagus has markedly improved prognosis. Many patients with short segments of Barrett's mucosa near the esophagogastric junction remain undiagnosed and at risk for the development of Barrett's adenocarcinomas (BA). Sucrase isomaltase (SI), an intestinal enzyme, is highly expressed in intestinal-type Barrett's mucosa and frequently expressed in dysplastic Barrett's mucosa and BA. Sucrose isomaltase is not expressed in normal esophageal or gastric mucosa. Alterations in the p53 tumor suppressor gene are frequent events in dysplastic Barrett's mucosa and BA and result in nuclear protein accumulation. The purpose of this study was to determine the presence or absence of these markers of Barrett's mucosa in adenocarcinoma of the esophagogastric junction or cardia.

METHODS

Expression of SI and p53 were examined in 40 BAs and 25 cardia adenocarcinomas using immunohistochemical techniques.

RESULTS

Sucrose isomaltase analysis revealed positive staining in 55% (22/40) of the BAs and 44% (11/25) of the cardia adenocarcinomas. Of 14 cardia adenocarcinomas that were SI negative, 100% (14/14) had no associated Barrett's mucosa. However, in 21 cardia adenocarcinomas with no associated Barrett's mucosa, 7/21 (33%) were SI positive. This suggests that SI-positive tumors may represent BA without the standard definition of Barrett's esophagus being met. P53 was present in 65% of BAs and 64% of cardia adenocarcinomas, demonstrating the importance and similarity of this gene alteration in both tumor types. Staining was positive for SI or p53 in 77% (50/65) of all tumors. Tumors of lower stage expressed SI more often than higher stage tumors.

CONCLUSIONS

These data suggest that a subset of cardia adenocarcinomas represent BAs. Surveillance endoscopy incorporating additional esophagogastric junction biopsies and assessment of SI or p53 may improve detection of intestinalized Barrett's mucosa and early dysplastic changes.

摘要

背景

对巴雷特食管患者的发育异常上皮进行常规监测已显著改善了预后。许多食管胃交界处附近有短节段巴雷特黏膜的患者仍未被诊断出来，存在发生巴雷特腺癌（BA）的风险。蔗糖异麦芽糖酶（SI）是一种肠道酶，在肠型巴雷特黏膜中高度表达，在发育异常的巴雷特黏膜和BA中也经常表达。正常食管或胃黏膜中不表达蔗糖异麦芽糖酶。p53肿瘤抑制基因的改变在发育异常的巴雷特黏膜和BA中是常见事件，并导致核蛋白积累。本研究的目的是确定食管胃交界处或贲门腺癌中是否存在这些巴雷特黏膜标志物。

方法

采用免疫组织化学技术检测40例BA和25例贲门腺癌中SI和p53的表达。

结果

蔗糖异麦芽糖酶分析显示，55%（22/40）的BA和44%（11/25）的贲门腺癌呈阳性染色。在14例SI阴性的贲门腺癌中，100%（14/14）没有相关的巴雷特黏膜。然而，在21例没有相关巴雷特黏膜的贲门腺癌中，7/21（33%）为SI阳性。这表明SI阳性肿瘤可能代表未达到巴雷特食管标准定义的BA。65%的BA和64%的贲门腺癌中存在p53，表明该基因改变在两种肿瘤类型中的重要性和相似性。所有肿瘤中有77%（50/65）的SI或p53染色呈阳性。低分期肿瘤比高分期肿瘤更常表达SI。