目的：高微卫星不稳定性（MSI-H）的结直肠癌（CRCs）是结直肠癌中的一个独特组。本研究调查了常见信号通路中基因突变及其在MSI-H CRC中的潜在临床意义。材料和方法：从384个原发性CRC中选择了25个MSI-H肿瘤，并从病历中收集了相关的临床和病理信息。使用商业套件和下一代测序（NGS）检测这些肿瘤中关键致癌基因的突变状态。使用原位杂交荧光染色和免疫组化验证NGS的结果。结果：本研究中，MSI-H占原发性CRC的6.51％，具有特殊的临床病理特征。NGS显示在目标基因中，平均每个肿瘤的突变数量为3.36，范围从1到9。在MSI-H CRCs中，有17个病例（68％）发生了RAS-RAF通路突变和18个病例（72％）发生了PI3K通路突变。其余两个病例包括EMAP样4-ALK受体酪氨酸激酶（EML4-ALK）融合和一个Erb-B2受体酪氨酸激酶2（ERBB2）错义突变。结论：本研究发现MSI-H CRCs中不同信号通路中多种变异相互存在，表明这种异质性肿瘤组需要复杂的治疗策略。因此，建议对这些患者进行额外的临床分子检测，如NGS，以确定适当的治疗策略。

Aims: Colorectal carcinomas with microsatellite instability high (MSI-H) are a distinctive group among colorectal cancers (CRCs). This study investigated the mutations of genes in the common signaling pathways and their potential clinical implications in MSI-H CRC. Materials and Methods: Twenty-five MSI-H tumors were selected from 384 primary CRCs, and the related clinical and pathological information were also collected from medical records. A commercial kit was used to detect the mutational status of crucial oncogenes within these tumors using next generation sequencing (NGS). Fluorescence in situ hybridization and immunohistochemistry were used to validate the NGS findings. Result: In the present study, MSI-H cases accounted for 6.51% of primary CRCs, with special clinicopathological features. NGS showed that the average number of mutations per tumor in the target genes evaluated was 3.36 and ranged from 1 to 9. In total, there were 17 cases (68%) with mutations in the RAS-RAF pathway and 18 cases (72%) with mutations in the PI3K pathway among the MSI-H CRCs. The remaining two cases included an EMAP Like 4-ALK Receptor Tyrosine Kinase (EML4-ALK) fusion and one with a Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2) missense mutation. Conclusion: This study found multiple variants within different signaling pathways that were mutually present in MSI-H CRCs, suggesting that such a heterogeneous group of tumors requires complex treatment responses. Thus, additional clinical molecular testing is recommended for such patients, such as NGS, to inform the appropriate treatment strategies.