Similar articles

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.

[1]An, C., Choi, I.S., Yao, J.C., Worah, S., Xie, K., Mansfield, P.F., Ajani, J.A., Rashid, A., Hamilton, S.R., Wu, T.T., 2005. Prognostic significance of CpG island methylator phenotype and microsatellite instability in gastric carcinoma. Clin. Cancer. Res., 11(2):656-663.

[2]Bacher, J.W., Flanagan, L.A., Smalley, R.L., Nassif, N.A., Burgart, L.J., Halberg, R.B., Megid, W.M., Thibodeau, S.N., 2004. Development of a fluorescent multiplex assay for detection of MSI-high tumors. Dis. Markers, 20(4-5):237-250.

[3]Berginc, G., Glavac, D., 2009. Rapid and accurate approach for screening of microsatellite unstable tumours using quasimonomorphic mononucleotide repeats and denaturating high performance liquid chromatography (DHPLC). Dis. Markers, 26(1):19-26.

[4]Boland, C.R., Thibodeau, S.N., Hamilton, S.R., Sidransky, D., Eshleman, J.R., Burt, R.W., Meltzer, S.J., Rodriguez-Bigas, M.A., Fodde, R., Ranzani, G.N., et al., 1998. A national cancer institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res., 58(22):5248-5257.

[5]Buhard, O., Suraweera, N., Lectard, A., Duval, A., Hamelin, R., 2004. Quasimonomorphic mononucleotide repeats for high-level microsatellite instability analysis. Dis. Markers, 20(4-5):251-257.

[6]de la Chapelle, A., 1999. Testing tumors for microsatellite instability. Eur. J. Hum. Genet., 7(4):407-408.

[7]Deng, G., Chen, A., Hong, J., Chae, H.S., Kim, Y.S., 1999. Methylation of CpG in a small region of the hMLH1 promoter invariably correlates with the absence of gene expression. Cancer Res., 59(9):2029-2033.

[8]Fang, D.C., Wang, R.Q., Yang, S.M., Yang, J.M., Liu, H.F., Peng, G.Y., Xiao, T.L., Luo, Y.H., 2003. Mutation and methylation of hMLH1 in gastric carcinomas with microsatellite instability. World J. Gastroenterol., 9(4):655-659.

[9]Forster, H.P., Emanuel, E., Grady, C., 2001. The 2000 revision of the Declaration of Helsinki: a step forward or more confusion? Lancet, 358(9291):1449-1453.

[10]Grady, W.M., 2004. Genomic instability and colon cancer. Cancer Metastasis Rev., 23(1-2):11-27.

[11]Gu, M., Kim, D., Bae, Y., Choi, J., Kim, S., Song, S., 2009. Analysis of microsatellite instability, protein expression and methylation status of hMLH1 and hMSH2 genes in gastric carcinomas. Hepatogastroenterology, 56(91-92):899-904.

[12]Li, F.Y., Lai, M.D., 2009. Colorectal cancer, one entity or three. J. Zhejiang Univ.-Sci. B, 10(3):219-229.

[13]Lim, S.B., Jeong, S.Y., Lee, M.R., Ku, J.L., Shin, Y.K., Kim, W.H., Park, J.G., 2004. Prognostic significance of microsatellite instability in sporadic colorectal cancer. Int. J. Colorectal Dis., 19(6):533-537.

[14]Lubbe, S.J., Webb, E.L., Chandler, I.P., Houlston, R.S., 2009. Implications of familial colorectal cancer risk profiles and microsatellite instability status. J. Clin. Oncol., 27(13):2238-2244.

[15]Ma, Y., Wu, L., Liu, C., Xu, L., Li, D., Li, J.C., 2009. The correlation of genetic instability of PINX1 gene to clinico-pathological features of gastric cancer in the Chinese population. J. Cancer Res. Clin. Oncol., 135(3):431-437.

[16]Murphy, K.M., Zhang, S., Geiger, T., Hafez, M.J., Bacher, J., Berg, K.D., Eshleman, J.R., 2006. Comparison of the microsatellite instability analysis system and the Bethesda panel for the determination of microsatellite instability in colorectal cancers. J. Mol. Diagn., 8(3):305-311.

[17]Oda, S., Zhao, Y., Maehara, Y., 2005. Microsatellite instability in gastrointestinal tract cancers: a brief update. Surg. Today, 35(12):1005-1015.

[18]Pawlik, T.M., Raut, C.P., Rodriguez-Bigas, M.A., 2004. Colorectal carcinogenesis: MSI-H versus MSI-L. Dis. Markers, 20(4-5):199-206.

[19]Sargent, D.J., Marsoni, S., Monges, G., Thibodeau, S.N., Labianca, R., Hamilton, S.R., French, A.J., Kabat, B., Foster, N.R., Torri, V., et al., 2010. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J. Clin. Oncol., 28(20):3219-3226.

[20]Seo, H.M., Chang, Y.S., Joo, S.H., Kim, Y.W., Park, Y.K., Hong, S.W., Lee, S.H., 2009. Clinicopathologic characteristics and outcomes of gastric cancers with the MSI-H phenotype. J. Surg. Oncol., 99(3):143-147.

[21]Suraweera, N., Duval, A., Reperant, M., Vaury, C., Furlan, D., Leroy, K., Seruca, R., Iacopetta, B., Hamelin, R., 2002. Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR. Gastroenterology, 123(6):1804-1811.

[22]Theuer, C.P., Campbell, B.S., Peel, D.J., Lin, F., Carpenter, P., Ziogas, A., Butler, J.A., 2002. Microsatellite instability in Japanese vs. European American patients with gastric cancer. Arch. Surg., 137(8):960-965.

[23]Umar, A., Boland, C.R., Terdiman, J.P., Syngal, S., Chapelle, A., Rüschoff, J., Fishel, R., Lindor, N.M., Burgart, L.J., Hamelin, R., et al., 2004. Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (lynch syndrome) and microsatellite instabilit. J. Natl. Cancer Inst., 96(4):261-268.

[24]Vita, F.D., Giuliani, F., Galizia, G., Belli, C., Aurilio, G., Santabarbara, G., Ciardiello, F., Catalano, G., Orditura, M., 2007. Neo-adjuvant and adjuvant chemotherapy of gastric cancer. Ann. Onc., 18(Suppl. 6):120-123.

[25]Xiao, Y.P., Wu, D.Y., Xu, L., Xin, Y., 2006. Loss of heterozygosity and microsatellite instabilities of fragile histidine triad gene in gastric carcinoma. World J. Gastroenterol., 12(23):3766-3769.

[26]Yuan, Y., Huang, Y.Q., Cai, S.R., Song, Y.M., Zheng, S., Zhang, S.Z., 2004. Genetic characterization of Chinese hereditary non-polyposis colorectal cancer by DHPLC and multiplex PCR. Jpn. J. Clin. Oncol., 34(11):660-666.