文章：

胆囊癌：一个罕见肿瘤的教训

Gallbladder cancer: lessons from a rare tumour

原文发布日期：2004-09-01

DOI: 10.1038/nrc1429

类型: Review Article

开放获取: 否

要点：

1. Gallbladder cancer is a relatively rare neoplasm worldwide, but shows significant geographic variation in incidence, being particularly common in certain native American populations. The prognosis for patients with this neoplasm is poor, as diagnosis is often at late, untreatable stages of the disease.
2. A unique combination of predisposing factors makes gallbladder carcinoma a unique tumour and offers potential for understanding cancer pathogenesis. These factors include ethnicity, genetic predisposition, geographic location, female gender, chronic inflammation and congenital developmental abnormalities.
3. Two main pathways of gallbladder carcinoma pathogenesis have been identified. The most common is associated with gallstones and chronic inflammation of the gallbladder, whereas a second, less frequent pathway is associated with a congenital abnormality of the pancreatic bile-duct junction, which is particularly common in Japan.
4. A multistage sequence of histopathological and molecular changes has been identified for gallbladder carcinoma, which is especially well-defined for tumorigenesis associated with gallstones. Molecular abnormalities commence in normal-appearing epithelium in chronically inflamed gallbladders.
5. TP53 inactivation has an important and early role in gallbladder carcinoma associated with gallstones and chronic inflammation. Different patterns of TP53 mutation have been detected in the two main types of gallbladder carcinomas that have been identified.
6. Although KRAS mutations are rarely detected in gallbladder carcinomas associated with gallstones, they are frequent and early events in tumours associated with congenital abnormality of the pancreatic bile-duct junction.
7. Relatively little is known about gallbladder cancer, and a significant influx of research funding is required for this to be remedied. In particular, the identification of susceptibility genes, elucidation of the role of inflammation and an increased understanding of the molecular changes that occur during multistage pathogenesis should be important goals for the future.

要点翻译：

1. 胆囊癌在全球范围内是一种相对罕见的肿瘤，但其发病率存在显著的地域差异，在某些美洲原住民群体中尤为常见。该肿瘤患者预后较差，因为诊断往往处于疾病晚期、无法治疗的阶段。
2. 独特的易感因素组合使胆囊癌成为一种特殊的肿瘤，并为理解癌症发病机制提供了潜力。这些因素包括种族、遗传易感性、地理位置、女性性别、慢性炎症和先天性发育异常。
3. 目前已确定胆囊癌发病的两条主要途径。最常见的一条与胆结石和胆囊慢性炎症相关，而第二条较少见的途径则与胰胆管合流异常这一先天性畸形有关，后者在日本尤为常见。
4. 研究已明确了胆囊癌多阶段演进过程中的组织病理学和分子改变序列，其中与胆结石相关的肿瘤发生途径尤其清晰。分子异常始于慢性炎症胆囊中外观正常的黏膜上皮。
5. TP53失活在胆结石及慢性炎症相关的胆囊癌中起着重要且早期的作用。在已确定的两种主要胆囊癌类型中，检测到TP53突变的不同模式。
6. 尽管KRAS突变在胆结石相关胆囊癌中很少检测到，但在胰胆管合流异常相关肿瘤中却是常见且早期的事件。
7. 目前对胆囊癌的了解相对较少，需要大量研究资金的投入来改善这一状况。特别是识别易感基因、阐明炎症的作用以及加深对多阶段发病机制中分子变化的理解，应成为未来的重要目标。

英文摘要：

Gallbladder cancer is a relatively rare form of malignancy about which our knowledge is scant. However, a unique combination of predisposing factors — including genetic predisposition, geographic distribution, female gender bias, chronic inflammation and congenital developmental abnormalities — makes this type of cancer unique and offers potential for understanding cancer pathogenesis in general. An understanding of how these risk factors contribute to the molecular basis of the disease is essential for understanding the origins of this unusual cancer.

摘要翻译： 

胆囊癌是一种相对罕见的恶性肿瘤，我们对其了解甚少。然而，其独特的易感因素组合——包括遗传倾向、地理分布、女性性别倾向、慢性炎症和先天性发育异常——使得这种癌症具有独特性，并为理解癌症发病机制提供了潜在途径。理解这些风险因素如何促成该疾病的分子基础，对于揭示这一罕见癌症的起源至关重要。

原文链接：

Gallbladder cancer: lessons from a rare tumour