Qualitative and Quantitative Aspects of Discrepancies between Various Methods for Microsatellite Instability Detection
By:
References
- Stelloo E, Jansen AML, Osse EM, Nout RA, Creutzberg CL, Ruano D, Church DN, Morreau H, Smit VTHBM, van Wezel T, Bosse T. Practical guidance for mismatch repair-deficiency testing in endometrial cancer. Annals of Oncology. 2017;28(1):96–102.
- Hissong E, Crowe EP, Yantiss RK, Chen Y-T. Assessing colorectal cancer mismatch repair status in the modern era: a survey of current practices and re-evaluation of the role of microsatellite instability testing. Modern Pathology. 2018;31(11):1756–66.
- Watson P, Vasen HFA, Mecklin J-P, Bernstein I, Aarnio M, Järvinen HJ, Myrhøj T, Sunde, L, Wijnen JT and Lynch HT. The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome. Int. J. Cancer. 2008;123(2):444–449.
- Overman MJ, Ernstoff MS, Morse MA. Where we stand with immunotherapy in colorectal cancer: deficient mismatch repair, proficient mismatch repair, and toxicity management. American Society of Clinical Oncology Educational Book. 2018:39–247
- Jin Z, Sinicrope FA. Mismatch Repair-Deficient Colorectal Cancer: Building on checkpoint blockade. Journal of Clinical Oncology. 2022;40(24):2735–50.
- Goel A, Nagasaka T, Hamelin R, Boland CR. An optimized pentaplex PCR for detecting DNA mismatch repair-deficient colorectal cancers. PLoS One. 2010;5(2):e9393. doi: 10.1371/journal.pone.0009393.
- Engel KB, Moore HM. Effects of preanalytical variables on the detection of proteins by immunohistochemistry in formalin-fixed, paraffin-embedded tissue. Arch Pathol Lab Med. 2011;135(5):537–43.
- Dedeurwaerdere F, Claes KB, Van Dorpe J, Rottiers I, Van der Meulen J, Breyne J, Swaerts K, Martens G. Comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer. Scientific Reports. 2021;11(1):12880.
- Guyot D’Asnières De Salins A, Tachon G, Cohen R, Karayan-Tapon L, Junca A, Frouin E, Godet J, Evrard C, Randrian V, Duval A, Svrcek M, Lascols O, Vignot S, Coulet F, André T, Fléjou JF, Cervera P, Tougeron D. Discordance between immunochemistry of mismatch repair proteins and molecular testing of microsatellite instability in colorectal cancer. ESMO Open. 2021;6(3):100120.
- Piñol V, Castells A, Andreu M, Castellví-Bel S, Alenda C, Llor X, Xicola RM, Rodríguez-Moranta F, Payá A, Jover R, Bessa X. Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer. JAMA. 2005;293(16):1986–94.
- Cohen R, Hain E, Buhard O, Guilloux A, Bardier A, Kaci R, et al. Assessment of local clinical practice for testing of mismatch repair deficiency in metastatic colorectal cancer: The need for new diagnostic guidelines prior to immunotherapy. Annals of Oncology. 2018;29:179–180.
- Yuan L, Chi Y, Chen W, Chen X, Wei P, Sheng W, Zhou X, Shi D. Immunohistochemistry and microsatellite instability analysis in molecular subtyping of colorectal carcinoma based on mismatch repair competency. International Journal of Clinical and Experimental Medicine. 2015;8(11):20988–21000.
- Yu F, Makrigiorgos A, Leong KW, Makrigiorgos GM. Sensitive detection of microsatellite instability in tissues and liquid biopsies: Recent developments and updates. Comput Struct Biotechnol J. 2021;19:4930–4943.
- Chen ML, Chen JY, Hu J, Chen Q, Yu LX, Liu BR, Qian XP, Yang M. Comparison of microsatellite status detection methods in colorectal carcinoma. Int J Clin Exp Pathol. 2018;11(3):1431–1438.
- Bonneville R, Krook MA, Chen HZ, Smith A, Samorodnitsky E, Wing MR, Reeser JW, Roychowdhury S. Detection of microsatellite instability biomarkers via next-generation sequencing. Methods Mol Biol. 2020;2055:119–132
- Ali-Fehmi R, Krause HB, Morris RT, Wallbillich JJ, Corey L, Bandyopadhyay S, Kheil M, Elbashir L, Zaiem F, Quddus MR, Abada E, Herzog T, Karnezis AN, Antonarakis ES, Kasi PM, Wei S, Swensen J, Elliott A, Xiu J, Hechtman J, Spetzler D, Abraham J, Radovich M, Sledge G, Oberley MJ, Bryant D. Analysis of concordance between next-generation sequencing assessment of microsatellite instability and immunohistochemistry-mismatch repair from solid tumors. JCO Precis Oncol. 2024;8:e2300648.
- Kang SY, Kim DG, Ahn S, Ha SY, Jang KT, Kim KM. Comparative analysis of microsatellite instability by next-generation sequencing, MSI PCR and MMR immunohistochemistry in 1942 solid cancers. Pathol Res Pract. 2022;233:153874.
- Staninova-Stojovska M, Matevska-Geskovska N, Panovski M, Angelovska B, Mitrevski N, Ristevski M, Jovanovic R, Dimovski AJ. Molecular basis of inherited colorectal carcinomas in the macedonian population: an update. Balkan J Med Genet. 2019;22(2):5–16.
- Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, Srivastava S. 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 research. 1998;58(22):5248–57.
- Berg KD, Glaser CL, Thompson RE, Hamilton SR, Griffin CA, Eshleman JR. Detection of microsatellite instability by fluorescence multiplex polymerase chain reaction. The Journal of molecular diagnostics : JMD. 2000;2(1):20–28.
- Pagin A, Zerimech F, Leclerc J, Wacrenier A, Lejeune, S; Descarpentries C, Escande F, Porchet N, Buisine M-P. Evaluation of a new panel of six mononucleotide repeat markers for the detection of DNA mismatch repair-deficient tumours. British Journal of Cancer. 2013;108(10):2079–2087.
- Pérez-Carbonell L, Alenda C, Payá A, Castillejo A, Barberá VM, Guillén C, Rojas E, Acame N, Gutiérrez-Aviñó FJ, Castells A, Llor X, Andreu M, Soto J-L, Jover R. Methylation analysis of MLH1 improves the selection of patients for genetic testing in Lynch Syndrome. J Mol Diagn. 2010;12(4):498–504.
- Jia P, Yang X, Guo L, Liu B, Lin J, Liang H, et al. MSIsensor-pro: fast, accurate, and matched-normal-sample-free detection of microsatellite instability. Genomics Proteomics Bioinformatics. 2020;18(1):65–71.
- Belvederesi L, Bianchi F, Loretelli C, Gagliardini D, Galizia E, Bracci R, Rosati S, Bearzi I, Viel A, Cellerino R, Porfiri E. Assessing the pathogenicity of MLH1 missense mutations in patients with suspected hereditary nonpolyposis colorectal cancer: correlation with clinical, genetic and functional features. Eur J Hum Genet. 2006;14(7):853–859.
- Bosch DE, Yeh MM, Salipante SJ, Jacobson A, Cohen SA, Konnick EQ, et al. Isolated MLH1 loss by immunohistochemistry because of benign germline MLH1 polymorphisms. JCO Precision Oncology. 2022(6):e2200227. doi: 10.1200/PO.22.00227.
- Shia J. Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part I. The utility of immunohistochemistry. The Journal of Molecular Diagnostics : JMD. 2008;10(4):293–300.
- Helderman N, Strobel, Bohaumilitzky L, Terlouw D, van der Werf – ’t Lam AM, van Wezel T, Morreau H, Knebel T, Nielsen M, Kloor M. Lower degree of microsatellite instability in colorectal carcinomas from MSH6-associated Lynch syndrome patients, Modern Pathology. 2025;100757:0893–3952.
https://doi.org/10.1016/j.modpat.2025.100757 . In press - Acharya S, Wilson T, Gradia S, Kane MF, Guerrette S, Marsischky GT, Kolodner R, Fishel R. hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6. Proceedings of the National Academy of Sciences of the United States of America. 1996;93(24):13629–13634.
- Ukkola I, Nummela P, Pasanen A, Kero M, Lepistö A, Kytölä S, Bützow R, Ristimäki A. Detection of microsatellite instability with Idylla MSI assay in colorectal and endometrial cancer. Virchows Arch. 2021;479(3):471–479.
- Siemanowski J, Schömig-Markiefka B, Buhl T, Haak A, Siebolts U, Dietmaier W, Arens N, Pauly N, Ataseven B, Büttner R, Merkelbach-Bruse S. Managing difficulties of microsatellite instability testing in endometrial cancer-limitations and advantages of four different PCR-based approaches. Cancers. 2021;13(6):1268
- Zhao YS, Hu FL, Wang F, Han B, Li DD, Li XW, Zhu S. Meta-analysis of MSH6 gene mutation frequency in colorectal and endometrial cancers. Journal of Toxicology and Environmental Health Part A. 2009;72(11-12):690–697.
- Dedeurwaerdere F, Claes KB, Van Dorpe J, Rottiers I, Van der Meulen J. Comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer. Sci Rep. 2021;11(1):12880
- Vikas P, Messersmith H, Compton C, Sholl L, Broaddus RR, Davis A, Estevez-Diz M, Garje R, Konstantinopoulos PA, Leiser A, Mills AM, Norquist B, Overman MJ, Sohal D, Turkington RC, Johnson T. Mismatch repair and microsatellite instability testing for immune checkpoint inhibitor therapy: ASCO endorsement of College of American Pathologists Guideline. J Clin Oncol. 2023;41(10):1943–1948.
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. Version 1.2025. NCCN; 2025. Available at:
https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1428 . Accessed March 22, 2025. - Niu CG, Zhang J, Rao AV, Joshi U, Okolo P. Comparative effectiveness of immunotherapy and chemotherapy in patients with metastatic colorectal cancer stratified by microsatellite instability status. World J Clin Oncol. 2024;15(4):540–547.
- Petrelli F, Ghidini M, Ghidini A, Tomasello G. Outcomes Following Immune checkpoint inhibitor treatment of patients with microsatellite instability-high cancers: a systematic review and meta-analysis. JAMA Oncol. 2020;6(7):1068–1071.
- Heregger R, Huemer F, Steiner M, Gonzalez-Martinez A, Greil R, Weiss L. Unraveling resistance to immunotherapy in MSI-high colorectal cancer. Cancers (Basel). 2023;15(20):5090.
- Huyghe N, Benidovskaya E, Stevens P, Van den Eynde M. Biomarkers of response and resistance to immunotherapy in microsatellite stable colorectal cancer: toward a new personalized medicine. Cancers (Basel). 2022;14(9):2241.
- Swaerts K, Dedeurwaerdere F, De Smet D, De Preter K, Vandesompele J. DeltaMSI: artificial intelligence-based modeling of microsatellite instability scoring on next-generation sequencing data. BMC Bioinformatics. 2023; 24:73.
- Wang Q, Yu M, Zhang S. The characteristics of the tumor immune microenvironment in colorectal cancer with different MSI status and current therapeutic strategies. Frontiers in Immunology, 2025, 15: 1440830.
DOI: https://doi.org/10.2478/bjmg-2025-0009 | Journal eISSN: 2199-5761
Language: English
Published on: Oct 8, 2025
Published by: Macedonian Academy of Sciences and Arts
In partnership with: Paradigm Publishing Services
Publication frequency: 2 times per year
Related subjects:
© 2025 M Staninova-Stojovska, N Matevska-Geshkovska, E Krstevska-Bozhinovikj, R Jovanovic, K Kubelka Sabit, B Angelovska, N Mitreski, P Noveski, A Dimovski, published by Macedonian Academy of Sciences and Arts
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.