Matsumoto N, Yoshida T, Yamashita K, Numata Y, Okayasu I
Department of Pathology, Kitasato University School of Medicine, Kitasato 1-15-1, Sagamihara, Kanagawa 228-8555, Japan.
Br J Cancer. 2003 Aug 18;89(4):707-12. doi: 10.1038/sj.bjc.6601141.
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.
结直肠癌肿瘤上皮和基质成分中的微卫星不稳定性（MSI）差异尚未得到充分研究。利用激光捕获显微切割技术，采集了40例散发性结直肠癌这些成分的单独样本，并用四种标记物检测了MSI。为了研究基质中MSI表型与其他基因事件及组织病理学特征之间的关系，分析了p53和K-ras基因突变，并通过免疫组织化学测定了p53、hMLH1和hMSH2蛋白的表达。上皮（34%）和基质组织（41%）均获得微卫星不稳定性阳性结果。上皮中的MSI与分化程度和Dukes分期相关，而基质中的MSI则呈相反关系，在高分化腺癌（54%）和Dukes A期病变（55%）中尤为常见。此外，还发现上皮中p53蛋白过表达与基质中MSI之间存在显著的负相关（P=0.02475）。结果提示，在结直肠癌发生过程中存在一种涉及基质遗传不稳定性的致癌替代途径。
