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Loss of DNA mismatch repair function has long been known in various malignancies, particularly colorectal cancer. However, microsatellite instability (MSI) testing was rarely requested in Thailand. Recently, the US Food and Drug Administration (FDA) has approved pembrolizumab, an antibody to PD-1 receptor, as an alternative treatment for high MSI (MSI-H) and/or MMR (mismatch repair)-deficient solid tumors. We report our recent observation on MSI testing in Thailand.
MATERIALS AND METHODS:
Data was collected from Chulalongkorn GenePRO Center, Faculty of Medicine, Chulalongkorn University, during July 2013 and July 2017. MSI testing was performed, using 5 microsatellite markers (BAT-25, BAT-26, D2S123, D5S346 and D17S250). The number, source, and result of samples underwent MSI assay were analyzed.
Requests for MSI testing have increased significantly in recent years. The shift started in 2015 when the MMR status was found to predict clinical benefit with the immune checkpoint blockade. There were 118 (75.2%) colorectal, 11 (7%) gastric, and 28 (17.8%) other cancers tested. MSI-H, MSI-L, and microsatellite stable (MSS) tumors were detected in 18 (11.5%), 11 (7%), and 128 (81.5%) patients, respectively. Of the 18 MSI-H cancers; 13 (72.2%), 4 (22.2%), and 1 (5.6%) were colorectal, gastric, and gynecologic malignancy, respectively. BAT25 and BAT26 markers were unstable in all MSI-H tumors.
We have experienced increasing demand for MSI testing in Thai patients at Chulalongkorn GenePRO Center. Colorectal cancers were most frequently tested, and accounted for the highest percentage among the MSI-H cancers.
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2. Choi YY, Bae JM, An JY, et al. Is microsatellite instability a prognostic marker in gastric cancer? A systematic review with meta-analysis. J Surg Oncol 2014;110(2):129-35.
3. Kloor M, Staffa L, Ahadova A, et al. Clinical significance of microsatellite instability in colorectal cancer. Langenbecks Arch Surg 2014;399(1):23-31.
4. Malesci A, Laghi L, Bianchi P, et al. Reduced likelihood of metastases in patients with microsatellite-unstable colorectal cancer. Clin Cancer Res 2007;13(13):3831-9.
5. Berg KD, Glaser CL, Thompson RE, et al. Detection of microsatellite instability by fluorescence multiplex polymerase chain reaction. J Mol Diagn 2000;2(1):20-8.
6. Boland CR, Thibodeau SN, Hamilton SR, et al. 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 1998;58(22): 5248-57.
7. Oh JR, Kim DW, Lee HS, et al. Microsatellite instability testing in Korean patients with colorectal cancer. Fam Cancer 2012;11(3):459-66.
8. Vaniawala S, Acharya A, Parekh H, et al. Pattern of variation in the mono- and dinucleotide repeat microsatellites associated with lynch syndrome in an Indian population. Oncol Res Treat 2014;37(12):720-4.
9. Zeinalian M, Emami MH, Salehi R, et al. Molecular analysis of Iranian colorectal cancer patients at risk for Lynch syndrome: a new molecular, clinicopathological feature. J Gastrointest Cancer 2015;46(2):118-25.
10. Gonzalez ML, Causada-Calo N, Santino JP, et al. Universal determination of microsatellite instability using BAT26 as a single marker in an Argentine colorectal cancer cohort. Fam Cancer 2017(2017):1-8.
11. Korphaisarn K, Pongpaibul A, Limwongse C, et al. Deficient DNA mismatch repair is associated with favorable prognosis in Thai patients with sporadic colorectal cancer. World J Gastroenterol 2015;21(3):926-34.
12. Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 2017;357(6349):409-13.
13. Viale G, Trapani D, Curigliano G. Mismatch repair deficiency as a predictive biomarker for immunotherapy efficacy. Biomed Res Int 2017(2017):1-7.
14. Chang L, Chang M, Chang HM, et al.Microsatellite instability: a predictive biomarker for cancer immunotherapy. Appl Immunohistochem Mol Morphol 2018;26(2):15-21.
15. Umar A, Boland CR, Terdiman JP, et al. Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 2004;96(4):261-8.
16. Le DT, Uram JN, Wang H, et al. PD-1 blockage in tumors with mismatch-repair deficiency. N Engl J Med 2015;372(26):2509-20.