Possible alternative carcinogenesis pathway featuring microsatellite instability in colorectal cancer stroma.

Possible alternative carcinogenesis pathway featuring microsatellite instability in colorectal cancer stroma.
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DOI:
10.1038/sj.bjc.6601141
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发表时间:
2003-08-18
影响因子:
8.8
通讯作者:
--
中科院分区:
医学1区
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--
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肿瘤上皮室和间质室的差异微卫星不稳定性(MSI)在结直肠癌中尚未得到很好的研究。采用激光捕获显微解剖技术,对40例散发性结直肠癌的不同隔室标本进行取样,并用四种标志物检测MSI。采用免疫组织化学方法检测P53和K-ras基因突变,并检测P53、hMLH1和hMSH2蛋白的表达,以探讨MSI表型与其他遗传事件和组织病理学特征之间的关系。上皮(34%)和间质组织(41%)的微卫星不稳定性结果均为阳性。上皮MSI与分化程度和Dukes‘s分期有关,而间质MSI与分化程度和Dukes’s分期呈负相关,在高分化腺癌(54%)和Dukes‘A病变(55%)中尤为常见。此外,P53蛋白在上皮中高表达与间质中微结构指数呈显著负相关(P=0.02475)。这些结果表明,在结直肠癌的发展过程中,另一种致癌途径涉及间质遗传不稳定性。
Differential microsatellite instability (MSI) in tumour epithelial and stromal compartments has not been well examined for colorectal cancers. Using laser-captured microdissection, separate specimens of these compartments of 40 sporadic colorectal cancers were sampled and MSI was tested with four markers. To examine the relation between the MSI phenotype in the stroma and other genetic events and histopathological features, p53 and K-ras gene mutations were analysed, and the expression of p53, hMLH1, and hMSH2 protein was determined by immunohistochemistry. Microsatellite instability positive results were obtained for both epithelium (34%) and stromal tissue (41%). While MSI in epithelium correlated with differentiation and Dukes' stage, that in stroma demonstrated an inverse relation, being particularly frequent in well-differentiated adenocarcinomas (54%) and Dukes' A lesions (55%). Further, a significant inverse correlation between p53 protein overexpression in the epithelium and MSI in the stroma was found (P=0.02475). The results suggest an alternative pathway of carcinogenesis involving stromal genetic instability in the development of colorectal cancers.
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发表时间: 2001-09-01
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