Wijnhoven B P, Tilanus H W, Dinjens W N
Department of Surgery, University Hospital Rotterdam, Erasmus University Rotterdam, Rotterdam, The Netherlands.
Ann Surg. 2001 Mar;233(3):322-37. doi: 10.1097/00000658-200103000-00005.
To review the current knowledge on the genetic alterations involved in the development and progression of Barrett's esophagus-associated neoplastic lesions.
Barrett's esophagus (BE) is a premalignant condition in which the normal squamous epithelium of the esophagus is replaced by metaplastic columnar epithelium. BE predisposes patients to the development of esophageal adenocarcinoma. Endoscopic surveillance can detect esophageal adenocarcinomas when they are early and curable, but most of the adenocarcinomas are detected at an advanced stage. Despite advances in multimodal therapy, the prognosis for invasive esophageal adenocarcinoma is poor. A better understanding of the molecular evolution of the Barrett's metaplasia to dysplasia to adenocarcinoma sequence may allow improved diagnosis, therapy, and prognosis.
The authors reviewed data from the published literature to address what is known about the molecular changes thought to be important in the pathogenesis of BE-associated neoplastic lesions.
The progression of Barrett's metaplasia to adenocarcinoma is associated with several changes in gene structure, gene expression, and protein structure. Some of the molecular alterations already showed promise as markers for early cancer detection or prognostication. Among these, alterations in the p53 and p16 genes and cell cycle abnormalities or aneuploidy appear to be the most important and well-characterized molecular changes. However, the exact sequence of events is not known, and probably multiple molecular pathways interact and are involved in the progression of BE to adenocarcinoma.
Further research into the molecular biology of BE-associated adenocarcinoma will enhance our understanding of the genetic events critical for the initiation and progression of Barrett's adenocarcinoma, leading to more effective surveillance and treatment.
综述目前关于巴雷特食管相关肿瘤性病变发生发展过程中基因改变的认识。
巴雷特食管（BE）是一种癌前病变，其中食管正常的鳞状上皮被化生的柱状上皮所取代。BE使患者易患食管腺癌。内镜监测可在食管腺癌早期且可治愈时检测到，但大多数腺癌是在晚期才被发现。尽管多模式治疗取得了进展，但侵袭性食管腺癌的预后仍然很差。更好地了解巴雷特化生至发育异常再至腺癌这一序列的分子演变，可能会改善诊断、治疗和预后。
作者回顾了已发表文献中的数据，以探讨在BE相关肿瘤性病变发病机制中被认为重要的分子变化。
巴雷特化生向腺癌的进展与基因结构、基因表达和蛋白质结构的多种变化有关。一些分子改变已显示出有望作为早期癌症检测或预后的标志物。其中，p53和p16基因的改变以及细胞周期异常或非整倍体似乎是最重要且特征明确的分子变化。然而，确切的事件顺序尚不清楚，可能有多种分子途径相互作用并参与BE向腺癌的进展。
对BE相关腺癌分子生物学的进一步研究将增进我们对巴雷特腺癌发生和进展关键基因事件的理解，从而实现更有效的监测和治疗。
