Tobi M
John D. Dingell Veterans Administration Medical Center, and Wayne State University School of Medicine, Detroit, MI 48201, USA.
Front Biosci. 1999 Mar 15;4:D329-38. doi: 10.2741/tobi.
Current understanding of colorectal carcinogenesis suggests a series of genetic changes occurring pari passu with morphological changes ultimately resulting in a cancerous lesion. The adenomatous polyp was originally the prototype of the preneoplastic lesion but recently, other colonic polyps, primarily the hamartomas, have been clinically characterized as colorectal cancer biomarkers with genetic changes found mainly in the mesenchymal component as opposed to the ectodermal, or epithelial element. This, with the current interest in angiogenesis playing a role in the propagation of neoplastic lesions, has now encompassed every tissue element and opened the way for an understanding of the oncogenic process. This has suggested that considerable interaction occurs between all tissue elements, including what was previously described as epithelial-matrix interactions. While hyperplastic polyps are thought not to confer risk for cancer, they may offer clues as to the first steps of the overall process. Microadenomas have introduced new clinical as well as biological considerations, as unique risk factors. Investigation of these lesions has moved from purely morphological correlations to mechanistic dissections of important biological pathways using both genetic and protein chemistry tools. This review explores the microcosm of the colonic polyp and its relation to cancer as the quintessential premalignant biomarker.
目前对结直肠癌发生机制的理解表明,一系列基因变化与形态学变化同步发生,最终导致癌性病变。腺瘤性息肉最初是癌前病变的原型,但最近,其他结肠息肉,主要是错构瘤,已被临床表征为结直肠癌生物标志物,其基因变化主要发生在间充质成分中,而非外胚层或上皮成分。随着当前对血管生成在肿瘤性病变增殖中作用的关注,这已涵盖了每个组织成分,并为理解致癌过程开辟了道路。这表明所有组织成分之间存在相当大的相互作用,包括以前描述的上皮-基质相互作用。虽然增生性息肉被认为不会增加患癌风险,但它们可能为整个过程的最初步骤提供线索。微腺瘤作为独特的风险因素,引入了新的临床和生物学考量。对这些病变的研究已从单纯的形态学关联转向使用基因和蛋白质化学工具对重要生物学途径进行机制剖析。本综述探讨结肠息肉的微观世界及其作为典型癌前生物标志物与癌症的关系。