Molecular And Clinical Pathology Features Of Hereditary Non-Polyposis Colorectal Cancer (HNPCC)

Objective: To analyses the molecular and clinical pathology features of hereditary non-polyposis colorectal cancer(HNPCC).Methods: We analyzed the mutation spectrum of the MLH1, MSH2 and MSH6 genes in a cohort of patients by PCR, DHPLC and sequencing and examined 4 reported single-nucleotide variants to identify single-nucleotide polymorphisms (SNPs), haplotypes, and the genotype-phenotype association with Chinese populations of 50 healthy individuals and 50 sporadic colorectal cancer patients by PCR-DHPLC. And we compare of the two categories of tumor-infiltrating lymphocytes- and analysis in relation to microsatellite instability (MSI). Results We identified 7 novel mutations(4 in hMLH1, one in hMSH2 and 2 in hMSH6) of 12 HNPCC Families and 4 variants (D132H, rsl2476364, rsl800152, rsl802577)were verified as SNPs .The genotype distribution for all four SNPs showed no association with sporadic colorectal cancer. Severe infiltration of intra-tumor cell-infiltrating lymphocytes (ITCIL) was observed in 53.8% of MSI-H HNPCC patients and 7.1% of MSI-L/MSS patients and there was a close correlation between ITCIL severity and increased microsatellite instability. Conclusion MSH6 seem to be a part of the mutation in HNPCC of our group and there was a close correlation between ITCIL severity and increased microsatellite instability.