Oliart Soledad, Martínez-Santos Cristina, Moreno-Azcoita Mariano, Cerquella Carlos, Nejda Nargisse, Daimiel Lydia, Iglesias Daniel, Fernández-Peralta Antonia M, González-Aguilera Juan J
Servicio de Cirugía, Hospital Central de la Cruz Roja San José y Santa Adela, Reina Victoria, Madrid, Spain.
Am J Clin Oncol. 2006 Aug;29(4):364-70. doi: 10.1097/01.coc.0000221428.35366.cb.
The mutator pathway implied in the development of colorectal cancer (CRC) is characterized by microsatellite instability (MSI). MSI tumors can be subdivided according to the level of instability: MSI-H (high), MSI-L (low) or stable MSS. MSI-H CRC displays a well described distinct phenotype, but the true biologic significance of MSI-L is still uncertain. The objective of this study was to further clarify if the MSI-L phenotype could reflect a distinct pathway of tumor development with a different clinical behavior.
We analyzed the clinicopathological and genetic variables of 156 patients with sporadic CRC in relation with the level of MSI of the tumors.
We have found that MSI-L tumors are someway in the middle of MSI-H and MSS CRC, as they share some features with each of the other 2 subgroups: left side location, lower incidence of LOH at MSH2 as MSS and Dukes B (stage II TNM) like MSI-H. Moreover, MSI-L tumors show higher incidence of KRAS mutations.
We believe that MSI-L tumors could be considered a distinct phenotype that develops through a "mild mutator pathway."
结直肠癌（CRC）发生过程中所涉及的突变途径以微卫星不稳定性（MSI）为特征。MSI肿瘤可根据不稳定程度进行细分：高度微卫星不稳定（MSI-H）、低度微卫星不稳定（MSI-L）或稳定的微卫星稳定（MSS）。MSI-H CRC表现出一种已被充分描述的独特表型，但MSI-L的真正生物学意义仍不明确。本研究的目的是进一步阐明MSI-L表型是否能反映具有不同临床行为的独特肿瘤发生途径。
我们分析了156例散发性CRC患者的临床病理和基因变量，并将其与肿瘤的MSI水平相关联。
我们发现MSI-L肿瘤在某种程度上处于MSI-H和MSS CRC之间，因为它们与其他两个亚组中的每一个都有一些共同特征：左侧位置、与MSS一样MSH2处低水平杂合性缺失（LOH）以及与MSI-H一样的Dukes B期（II期TNM）。此外，MSI-L肿瘤显示KRAS突变的发生率更高。
我们认为MSI-L肿瘤可被视为通过“轻度突变途径”发生的独特表型。
