Besides analyzing the frequency, providing clinical characteristics and performing conventional histology, immunohistochemistry, PCR-based MSI testing, testing for MLH1 promotor hypermethylation and BRAF exon 15 mutation, we additionally applied next-generation sequencing (NGS) focusing on genes related to DNA repair to further understand the molecular basis of dysregulated MLH1/PMS2 and MSH2/MSH6 expression among different digestive system cancer entities. The gene discussed is MSH6; the disease is digestive system cancer.