Koppert Linetta B, Wijnhoven Bas P L, van Dekken Herman, Tilanus Hugo W, Dinjens Winand N M
Department of Surgery, Erasmus MC, University Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
J Surg Oncol. 2005 Dec 1;92(3):169-90. doi: 10.1002/jso.20359.
Barrett's esophagus is an acquired metaplastic change that occurs in the distal esophagus secondary to chronic gastroesophageal reflux. This premalignant condition forms the most important risk factor for developing esophageal adenocarcinoma, which is an extremely aggressive tumor with a 5-year survival rate of less than 25%. Carcinomas that arise in the setting of Barrett's esophagus are thought to develop as part of the metaplasia-dysplasia-carcinoma sequence.
To review the current knowledge on the genomic alterations involved in the development of Barrett's esophagus and its progression to dysplasia and/or cancer.
Several changes in gene structure, gene expression, and protein structure are associated with the progression of Barrett's esophagus to adenocarcinoma. Accumulation of these changes seems to be essential, rather than the exact sequence of these changes. Multiple molecular pathways are involved and interact with each other. Alterations in tumor suppressor genes, amongst which p53 and p16, are early events in the metaplasia-dysplasia-adenocarcinoma sequence, followed by loss of cell cycle checkpoints. Ongoing genomic instability leads to cumulative genetic errors and thereby the generation of multiple clones of transformed cells.
Within the multistep process of esophageal adenocarcinogenesis, to date no single molecular marker came forward able to predict who will and who will not develop cancer in the setting of Barrett's esophagus. Instead, panels of markers need to be developed in the future allowing to indicate disease progression. Identification of crucial molecular pathways involved in esophageal adenocarcinogenesis would ultimately improve therapy and facilitate development of new treatment strategies.
巴雷特食管是一种后天获得性化生改变，继发于慢性胃食管反流，发生于食管远端。这种癌前病变是食管腺癌发生的最重要危险因素，食管腺癌是一种极具侵袭性的肿瘤，5年生存率低于25%。巴雷特食管背景下发生的癌被认为是化生-发育异常-癌序列的一部分。
综述目前关于巴雷特食管发生及其进展为发育异常和/或癌症过程中涉及的基因组改变的知识。
基因结构、基因表达和蛋白质结构的几种改变与巴雷特食管进展为腺癌有关。这些改变的积累似乎至关重要，而非这些改变的确切顺序。涉及多个分子途径，且它们相互作用。肿瘤抑制基因的改变，其中包括p53和p16，是化生-发育异常-腺癌序列中的早期事件，随后是细胞周期检查点的丧失。持续的基因组不稳定导致累积的遗传错误，从而产生多个转化细胞克隆。
在食管腺癌发生的多步骤过程中，迄今为止，没有单一分子标志物能够预测在巴雷特食管背景下谁会患癌，谁不会患癌。相反，未来需要开发标志物组合以指示疾病进展。识别食管腺癌发生中涉及的关键分子途径最终将改善治疗并促进新治疗策略的开发。
