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

ABSTRACT

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.