Yan-qin Huang1, Ying Yuan, Wei-ting Ge, Han-guang Hu, Su-zhan Zhang, Shu Zheng. 1. Key Laboratory of Cancer Prevention and Intervention of Ministry of Education, Key Laboratory of Molecular Biology in Medical Science of Zhejiang Province, Cancer Institute, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
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.
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 mononucleotideMSI 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.
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