Hruban R H, Wilentz R E, Goggins M, Offerhaus G J, Yeo C J, Kern S E
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Ann Oncol. 1999;10 Suppl 4:9-11.
An understanding of incipient pancreatic neoplasia is an essential foundation for the future development of effective screening tests for pancreatic cancer. Only when we understand early pancreatic neoplasms will we be able to detect tumors that are curable with surgical resection.
Two approaches have helped define incipient pancreatic neoplasia. First, the histologic examination of pancreata has helped identify the most common histologic lesions in pancreatic tissues adjacent to infiltrating carcinomas. The assumption is that some of these lesions represent the precursors to the infiltrating cancers. Second, advances in molecular genetics now make it possible to define the genetic alterations present in small lesions. The demonstration that a suspected precursor lesion and an infiltrating pancreatic carcinoma share the same genetic alterations would help establish that the lesion is indeed a precursor to infiltrating pancreatic carcinoma.
A spectrum of intraductal proliferations in the pancreas has been found associated with infiltrating adenocarcinoma of the pancreas. These lesions, called "duct lesions," have even been identified in pancreata years before patients develop infiltrating carcinoma. Molecular genetic analysis of these lesions has revealed that they frequently harbor many of the same alterations present in infiltrating carcinoma of the pancreas. These alterations include activation of K-ras and inactivation of p16, p53 and, rarely BRCA2.
From these morphologic and molecular observations, we can now develop a progression model for the development of infiltrating carcinoma of the pancreas. Infiltrating carcinomas of the pancreas may arise from pancreatic duct lesions, and the progression of duct lesions to infiltrating cancer is associated with the accumulation of generalized and specific genetic alterations.
了解早期胰腺肿瘤是未来开发有效的胰腺癌筛查测试的重要基础。只有当我们了解早期胰腺肿瘤时，我们才能检测出可通过手术切除治愈的肿瘤。
有两种方法有助于定义早期胰腺肿瘤。首先，胰腺的组织学检查有助于识别浸润性癌旁胰腺组织中最常见的组织学病变。假设这些病变中的一些代表浸润性癌的前体。其次，分子遗传学的进展现在使定义小病变中存在的基因改变成为可能。怀疑的前体病变和浸润性胰腺癌具有相同的基因改变，这一证明将有助于确定该病变确实是浸润性胰腺癌的前体。
已发现胰腺中的一系列导管内增生与胰腺浸润性腺癌相关。这些病变被称为“导管病变”，甚至在患者发生浸润性癌前数年就在胰腺中被发现。对这些病变的分子遗传学分析表明，它们经常具有许多与胰腺浸润性癌相同的改变。这些改变包括K-ras激活以及p16、p53失活，很少有BRCA2失活。
从这些形态学和分子观察中，我们现在可以建立一个胰腺浸润性癌发生发展的进展模型。胰腺浸润性癌可能起源于胰腺导管病变，导管病变向浸润性癌的进展与普遍和特定基因改变的积累有关。
