Comparative features of colorectal and gastric cancers with microsatellite instability in Chinese patients

Objective:The purpose of this study was to determine the unique and universal features of microsatellite instability-high(MSI-H) colorectal cancer(CRC) and MSI-H gastric cancer(GC) in the Chinese population.Methods:A new panel of mononucleotide MSI markers,BAT25,BAT26,NR21,NR24,and MONO-27,was used to define MSI status in 303 CRC and 288 GC subjects.Clinicopathological features of both types of MSI-H tumors were analyzed.Methylation analysis in the hMLH1 promoter region by methylation specific polymerase chain reaction(PCR) and mutation detection of hMSH2/hMLH1 genes by denaturing high-performance liquid chromatography(DHPLC) were carried out simultaneously.Results:MSI-H CRCs and MSI-H GCs account for 11.9% and 8.0% of unselected sporadic CRCs and GCs,respectively.MSI-H CRCs are strongly characterized by early onset,right-side location,low differentiation,mucinous tumor,less infiltration,less lymphatic metastasis,and more often familial tumor.MSI-H GCs only showed site preference for the antrum and less lymphatic metastasis.Genetic and epigenetic analyses were positive in 6/36 MSI-H CRCs and 0/23 MSI-H GCs with pathological mutation in major mismatch repair genes,and in 7/36 MSI-H CRCs and 18/23 MSI-H GCs with methylated hMLH1 promoter(P<0.01),respectively.Conclusions:Although there are many differences in the genetic basis and clinicopathological features between MSI-H CRC and MSI-H GC,when compared with their microsatellite stable(MSS) counterparts,site preference and lymphatic metastasis are features common to both types of MSI-H tumors.