Pathological analysis for premalignant lesions of colon cancer

人们普遍认为，结直肠癌的发生是一种典型的多步骤肿瘤发生过程，伴随着基因的改变。啮齿动物癌变易感结肠表面发现的异常隐窝病灶(Acf)被认为是早期出现的癌前病变。然而，目前还不清楚这种病变是否真的是啮齿动物结直肠癌的癌前病变。最近，我们在结肠癌发生的早期阶段发现了结肠粘膜中的β-连环蛋白蓄积性隐窝(BCAC)。在这个项目中，我们对啮齿动物的BCAC进行了进一步的分析。我们证明了Wnt信号通路的改变导致了BCAC的形成，而BCAC在结肠癌发生的早期阶段起着重要作用。我们的结果提供了进一步的证据，证明BCAC是啮齿动物结肠癌的癌前病变。我们还表明支链霉菌是结肠癌发生的可靠生物标志物。此外，我们还搜索了与人类结肠中的支气管状癌类似的发育不良病变。我们研究了大量人类结肠的组织切片。然而，在啮齿类动物中证实的这种损伤还没有在人类结肠粘膜中发现。现在，我们正在进行进一步的分析，以找出人类结肠中的支原体。我们检测了人小结直肠息肉中APC基因的突变谱，得到了一些有趣的结果。虽然结果是初步的，但我们相信这些数据为了解人类和啮齿动物的结肠癌前病变提供了重要线索。

It is widely believed that colorectal carcinogenesis is a representative multistep tumorigenesis with events of genetic alterations. Aberrant crypt foci (ACF) recognized in the surface of cancer-predisposed colons of rodents have been regarded as early-appearing preneoplastic lesions. However, it is not clear that such lesions are truly precancerous lesions for colorectal cancers in rodents. Recently, we have identified β-catenin-accumulated crypts (BCAC) in colonic mucosa at the early stages of colon carcinogenesis.In this project, we performed further analyses of BCAC in rodents. We demonstrated that alterations in Wnt signaling pathway result in the formation of BCAC, and BCAC play an important role during early stages of colon carcinogenesis. Our results provide additional evidences that BCAC are premalignant lesions of colon cancer in rodents. We also showed that BCAC are reliable biomarkers for colon carcinogenesis. In addition, we searched for the similar dysplastic lesions as BCAC in human colon. We investigated a large number of histological sections from human colons. However, such lesions confirmed in rodents have not yet identified in human colonic mucosa. Now, we are going on further analyses to find out BCAC in human colon. We determined mutation spectrum of APC gene in small human colonic polyps and got some interesting results. Although the results are preliminary, we believe that such data provide important clue to understand the premalignancy of colon cancer in humans as well as rodents.