Features of colorectal cancers with high-level microsatellite instability occurring in familial and sporadic settings - Parallel pathways of tumorigenesis
Features of colorectal cancers with high-level microsatellite instability occurring in familial and sporadic settings - Parallel pathways of tumorigenesis
复制标题
DOI：
10.1016/s0002-9440(10)63062-3
复制
发表时间：
2001-12-01
影响因子：
6
通讯作者：
Jass, JR
中科院分区：
文献类型：
--
作者：
Young, J;Simms, LA;Jass, JR
高水平微卫星不稳定性（AISI-H）在10%至15%的散发性结直肠癌和大多数遗传性非息肉病性结直肠癌（HNPCC）中得到证实。这些MSI-H癌症类别之间的区别具有临床重要性，本研究的目的是评估可能具有区分性的临床、病理和分子特征。将112例符合Bethesda标准的MSI-H结直肠癌家族与57例散发性MSI-H结直肠癌进行比较。HNPCC癌症在较低的年龄出现（P < 0.001），在57岁之前没有诊断出散发性MSI-H癌症。MSI在HNPCC中的分布范围较低，72%的微卫星标记显示条带移位，而在散发性肿瘤中为87%（P < 0.001）。仅在HNPCC肿瘤中发现hMSH 2免疫染色缺失。在87%的散发性癌症中观察到bMLH 1甲基化，但在55%的HNPCC肿瘤中也观察到hMLH 1表达缺失（P = 0.02）。HNPCC癌更常以异常β-连环蛋白免疫染色为特征，如核阳性所证明（P < 0.001）.异常p53免疫染色在两组中均不常见。5 q杂合性缺失和12号密码子K-ras突变在两组中均不常见。与RNPCC肿瘤相比，散发性MSI-H肿瘤更常见于异质性（P < 0.001）、低分化（P = 0.02）、粘液性（P = 0.02）和近端（P = 0.04）。在散发性MSI-H癌症中，连续腺瘤可能是锯齿状的，而传统腺瘤在HNPCC中占主导地位。淋巴细胞浸润在HNPCC中更明显，但结果未达到统计学意义。总体而言，HNPCC癌症在形态和β-连环蛋白表达方面更像普通结肠直肠癌，而散发性MSI-H癌症显示出与不同形态发生一致的特征。没有个体特征对所有RN-PCC癌症具有歧视性。然而，基于四个特征的模型能够将94.5%的肿瘤分类为散发性或HNPCC。散发性和家族性MSI-H结直肠癌在基因型和表型方面的多重差异的发现与通过平行进化途径的肿瘤发生一致，并强调了分别研究这两组的重要性。
High-level microsatellite instability (AISI-H) is demonstrated in 10 to 15% of sporadic colorectal cancers and in most cancers presenting In the inherited condition hereditary nonpolyposis colorectal cancer (HNPCC). Distinction between these categories of MSI-H cancer is of clinical importance and the aim of this study was to assess clinical, pathological, and molecular features that might he discriminatory. One hundred and twelve MSI-H colorectal cancers from families fulfilling the Bethesda criteria were compared with 57 sporadic MSI-H colorectal cancers. HNPCC cancers presented at a lower age (P < 0.001) with no sporadic MSI-H cancer being diagnosed before the age of 57 years. MSI was less extensive in HNPCC cancers with 72% microsatellite markers showing band shifts compared with 87% in sporadic tumors (P < 0.001). Absent immunostaining for hMSH2 was only found in HNPCC tumors. Methylation of bMLH1 was observed in 87% of sporadic cancers but also in 55% of HNPCC tumors that showed loss of expression of hMLH1 (P = 0.02). HNPCC cancers were more frequently characterized by aberrant beta -catenin immunostaining as evidenced by nuclear positivity (P < 0.001). Aberrant p53 immunostaining was infrequent in both groups. There were no differences with respect to 5q loss of heterozygosity or codon 12 K-ras mutation, which were infrequent in both groups. Sporadic MSI-H cancers were more frequently heterogeneous (P < 0.001), poorly differentiated (P = 0.02), mucinous (P = 0.02), and proximally located (P = 0.04) than RNPCC tumors. In sporadic MSI-H cancers, contiguous adenomas were likely to be serrated whereas traditional adenomas were dominant in HNPCC. Lymphocytic infiltration was more pronounced in HNPCC but the results did not reach statistical significance. Overall, HNPCC cancers were more like common colorectal cancer in terms of morphology and expression of beta -catenin whereas sporadic MSI-H cancers displayed features consistent with a different morphogenesis. No individual feature was discriminatory for all RN-PCC cancers. However, a model based on four features was able to classify 94.5% of tumors as sporadic or HNPCC. The finding of multiple differences between sporadic and familial MSI-H colorectal cancer with respect to both genotype and phenotype is consistent with tumorigenesis through parallel evolutionary pathways and emphasizes the importance of studying the two groups separately.