The genetic changes in association with tumor progression and biological behavior

与肿瘤进展和生物学行为相关的遗传变化

• 批准号: 09670191
• 负责人: YAO Takashi
• 金额: $ 1.79万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670191/
• 关键词: colorectal neoplasms; adenoma; serrated adenoma; gastric phenotype; gastric mucin; MUC2; CD10; p53; 大腸; 癌; 腺種; 細胞分化; 鋸歯状線腫; human gastric mucin; p52; P53; pS2

The serrated adenoma, one of the subtype of colorectal adenoma, grows in polypoid and flat configurations. In order to analyze the progression of early flat carcinoma, the serrated adenoma should be included in this study. The serrated adenoma, metaplastic polyp and adenocarcinoma arising from these lesions had a common histological features and expressed the same phenotype of gastric-type, although they were colonic lesions. We reported the unique cell lineage of them, which was different from that of usual tubular adenoma. On the other hand, the gastric-phenotype was recognized only in 3 % of randomly selected colorectal carcinomas. Therefore, this serrated polyp-carcinoma sequence was considered o be a peculiar carcinogenic pathway. Further examination of phenotypes on the villous adenoma, carcinoma arising in ulcerative colitis and carcinoma with liver metastasis elucidated the several carcinogenic pathways, and also revealed the highly malignant behavior of carcinoma with CD10 expression.It was suggested that p53 played a important role in carcinogenic pathway of the colorectal carcinoma with gastric-phenotype, but it did not in villous tumor, by immunohistochemical study on p53 protein overexpression. Further genetic analysis will be needed for precisely evaluating the biological behavior and clarifying the carcinogenic pathway.

锯齿状腺瘤是结直肠腺瘤的一种亚型，呈息肉样和扁平状生长。为了分析早期扁平癌的进展，锯齿状腺瘤应该包括在这项研究中。来自这些病变的锯齿状腺瘤、化生息肉和腺癌虽然是结肠病变，但具有共同的组织学特征，表现为与胃型相同的表型。我们报道了它们独特的细胞谱系，这与常见的管状腺瘤不同。另一方面，在随机选择的结直肠癌中，只有3%的人能识别出胃表型。因此，这种锯齿状的息肉-癌序列被认为是一种特殊的致癌途径。通过对绒毛状腺瘤、溃疡性结肠炎癌变和肝转移癌表型的进一步研究，阐明了CD10表达的几种致癌途径，揭示了CD10表达癌的高度恶性行为。通过对P53蛋白过表达的免疫组织化学研究，提示P53在胃表型结直肠癌的致癌途径中起重要作用，而在绒毛状癌中不起作用。需要进行进一步的遗传分析，以准确评估生物学行为并阐明致癌途径。

项目成果

Kabashima A, et al.: "Gastric or intestinal phenotypic expression in the carcinomas and background mucosa of multiple early gastric carcinomas"Histopathology. 37 (6). 513-522 (2000)

Kabashima A 等人：“多发性早期胃癌的癌和背景粘膜中的胃或肠表型表达”组织病理学。

Sugao Y, et al.: "The incidence of apoptosis during colorectal tumorigenesis"Int J Surg Pathol. 8(2). 123-32 (2000)

Sugao Y 等人：“结直肠肿瘤发生过程中细胞凋亡的发生率”Int J Surg Pathol。

Yao T, et al.: "Multiple 'serrated adenocarcinomas' of the colon with a cell lineage common to metaplastic polyp and serrated adenoma. Case report of a new subtype of colonic adenocarcinoma with gastric differentiation."Journal of Pathology. 190. 444-449

Yao T 等人：“结肠多发‘锯齿状腺癌’，其细胞谱系与化生性息肉和锯齿状腺瘤常见。结肠腺癌新亚型伴胃分化的病例报告。”病理学杂志。

Yao T, et al.: "Multiple serrated adenocarcinomas' of the colon with a cell lineage common to metaplastic polyp and serrated adenoma. Case report of a new subtype of colonic adenocarcinoma with gastric differentiation"Journal of Pathology. 190. 444-449 (2

Yao T 等人：“结肠多发性锯齿状腺癌，其细胞谱系与化生性息肉和锯齿状腺瘤常见。结肠腺癌新亚型伴胃分化的病例报告”病理学杂志。

Eguchi K, et al.: "Disordance of p53 mutations of synchronous colorectal carcinomas"Modern Pathology. 13(2). 131-139 (2000)

Eguchi K 等人：“同步结直肠癌的 p53 突变紊乱”现代病理学。