Pathological analysis for premalignant lesions of colon cancer

目前普遍认为，大肠癌的发生是一个具有代表性的多步骤的肿瘤发生与遗传改变的事件。在啮齿类动物易患癌症的结肠表面发现的异常隐窝灶（ACF）被认为是早期出现的癌前病变。然而，目前尚不清楚这种病变是否是啮齿动物结直肠癌的真正癌前病变。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-catenin-accumulated crypts（BCAC），本项目对啮齿类动物中的BCAC进行了进一步的分析。我们证明，Wnt信号通路的改变导致BCAC的形成，BCAC在结肠癌发生的早期阶段发挥重要作用。我们的研究结果提供了额外的证据，BCAC是啮齿动物结肠癌的癌前病变。我们还表明BCAC是结肠癌发生的可靠生物标志物。此外，我们还在人类结肠中寻找与BCAC相似的异型增生病变。我们研究了大量的人类结肠组织切片。然而，在啮齿类动物中证实的这种病变尚未在人类结肠粘膜中发现。现在，我们将进一步分析，以找出BCAC在人类结肠。我们对人结肠小息肉APC基因突变谱进行了检测，得到了一些有趣的结果。虽然这些结果是初步的，我们相信这些数据提供了重要的线索，以了解结肠癌的癌前病变在人类以及啮齿动物。

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.