Rice T W, Goldblum J R, Falk G W, Tubbs R R, Kirby T J, Casey G
Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Ohio 44195.
J Thorac Cardiovasc Surg. 1994 Dec;108(6):1132-7.
Barrett's esophagus is a metaplastic condition with an unpredictable potential for neoplasia. Mutations of the tumor-suppressor gene p53 have been implicated in the evolution of some carcinomas. These mutations frequently result in intranuclear protein accumulation, which can be detected immunohistochemically. This study was undertaken to determine whether p53 immunoreactivity in Barrett's esophagus is a marker of neoplasia and, if so, when it occurs in the metaplasia-dysplasia-carcinoma sequence. Twenty-eight esophageal resection specimens were studied. Barrett's mucosa was present in each specimen, low-grade dysplasia in 27, high-grade dysplasia in 26, intramucosal cancer in 18, and submucosal cancer in 5. Immunohistochemical staining with the monoclonal antibody Pab1801 was used to detect the intranuclear protein product of mutated p53. No p53 immunoreactivity was seen in specimens of Barrett's mucosa or low-grade dysplasia. p53 immunoreactivity was found only in specimens of high-grade dysplasia, intramucosal cancer, and submucosal cancer. Sixty-nine percent (18/26) of these specimens exhibited mutated p53; 18 of 26 specimens of high-grade dysplasia (69%), 12 of 18 intramucosal cancer specimens (67%), and two of five submucosal cancer specimens (40%) expressed mutated p53. When p53 staining was observed, the spectrum of neoplastic changes (high-grade dysplasia, intramucosal cancer, submucosal cancer) within the specimen was positive. We conclude that (1) p53 immunoreactivity in Barrett's esophagus is a frequent, but not inclusive, marker for high-grade dysplasia, intramucosal cancer, and submucosal cancer and (2) immunoreactivity occurs late in the metaplasia-dysplasia-carcinoma sequence, during the transition to high-grade dysplasia.
巴雷特食管是一种化生状态，具有不可预测的肿瘤形成潜能。肿瘤抑制基因p53的突变与某些癌症的进展有关。这些突变常常导致核内蛋白积聚，可通过免疫组织化学检测到。本研究旨在确定巴雷特食管中p53免疫反应性是否为肿瘤形成的标志物，如果是，它在化生-发育异常-癌序列中何时出现。研究了28例食管切除标本。每个标本均存在巴雷特黏膜，27例有低级别发育异常，26例有高级别发育异常，18例有黏膜内癌，5例有黏膜下癌。使用单克隆抗体Pab1801进行免疫组织化学染色以检测突变型p53的核内蛋白产物。在巴雷特黏膜或低级别发育异常的标本中未观察到p53免疫反应性。仅在高级别发育异常、黏膜内癌和黏膜下癌的标本中发现p53免疫反应性。这些标本中有69%（18/26）显示突变型p53；26例高级别发育异常标本中有18例（69%）、18例黏膜内癌标本中有12例（67%）、5例黏膜下癌标本中有2例（40%）表达突变型p53。当观察到p53染色时，标本内肿瘤性变化谱（高级别发育异常、黏膜内癌、黏膜下癌）均为阳性。我们得出结论：（1）巴雷特食管中的p53免疫反应性是高级别发育异常、黏膜内癌和黏膜下癌的常见但非唯一标志物；（2）免疫反应性在化生-发育异常-癌序列中出现较晚，发生在向高级别发育异常转变的过程中。
