Familial Cancer

, Volume 11, Issue 3, pp 459–466 | Cite as

Microsatellite instability testing in Korean patients with colorectal cancer

  • Jung Ryul Oh
  • Duck-Woo KimEmail author
  • Hye Seung Lee
  • Hee Eun Lee
  • Sung Min Lee
  • Je-Ho Jang
  • Sung-Bum Kang
  • Ja-Lok Ku
  • Seung-Yong Jeong
  • Jae-Gahb Park
Original Article


Microsatellite instability (MSI) testing is useful for identifying patients with hereditary nonpolyposis colorectal cancer and detecting sporadic colorectal cancer that develops through replication error pathways. A pentaplex panel is recommended by the National Cancer Institute for MSI testing, but simplified mononucleotide panels and immunohistochemistry of mismatch repair proteins are widely employed for convenience. This study was to evaluate the MSI status of colorectal cancer in Korean patients. This study included 1,435 patients with colorectal adenocarcinoma subjected to surgical resection. The pentaplex Bethesda panel was used for MSI testing. Seventy nine (5.5 %) carcinomas were classified as MSI-high (MSI-H) and 95 (6.6 %) as MSI-low (MSI-L). BAT-26 and BAT-25 were unstable in 73 and 75 of 79 MSI-H carcinomas, respectively. With the panel comprising these 2 mononucleotide markers, 72 carcinomas were diagnosed as MSI-H, compared to the Bethesda panel data (72/79, 91.1 %). In contrast, BAT-26 or BAT-25 were unstable in only 7 (7.4 %) of the 95 MSI-L tumors. In the panel with 2 dinucleotide markers, D17250 linked to p53 and D2S123 to hMSH2, detection rates were 89.9 % (71/79) for MSI-H and 80.0 % (76/95) for MSI-L carcinomas, compared to the Bethesda panel. Moreover, we compared the frequency of MSI tumor in our patients with those reported previously from Western countries. In conclusion, the frequency of MSI-H appears lower in colorectal cancer patients in Korea. A simplified panel for MSI testing with BAT-26 and BAT-25 seems not effective for the accurate evaluation of MSI status, particularly in MSI-L colorectal carcinomas, in our patients.


Colorectal cancer Ethnic difference Hereditary nonpolyposis colorectal cancer, HNPCC Microsatellite instability, MSI 



This study was supported by grants from the Korea Health Industry Development Institute (KHIDI Grant No. A101097).


  1. 1.
    Boland CR, Thibodeau SN, Hamilton SR 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 58:5248–5257PubMedGoogle Scholar
  2. 2.
    Umar A, Boland CR, Terdiman JP et al (2004) Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96:261–268PubMedCrossRefGoogle Scholar
  3. 3.
    Peltomaki P (2003) Role of DNA mismatch repair defects in the pathogenesis of human cancer. J Clin Oncol 21:1174–1179PubMedCrossRefGoogle Scholar
  4. 4.
    Ionov Y, Peinado MA, Malkhosyan S et al (1993) Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 363:558–561PubMedCrossRefGoogle Scholar
  5. 5.
    Shibata D, Peinado MA, Ionov Y et al (1994) Genomic instability in repeated sequences is an early somatic event in colorectal tumorigenesis that persists after transformation. Nat Genet 6:273–281PubMedCrossRefGoogle Scholar
  6. 6.
    Heinen CD, Richardson D, White R et al (1995) Microsatellite instability in colorectal adenocarcinoma cell lines that have full-length adenomatous polyposis coli protein. Cancer Res 55:4797–4799PubMedGoogle Scholar
  7. 7.
    Gologan A, Krasinskas A, Hunt J et al (2005) Performance of the revised Bethesda guidelines for identification of colorectal carcinomas with a high level of microsatellite instability. Arch Pathol Lab Med 129:1390–1397PubMedGoogle Scholar
  8. 8.
    Hoang JM, Cottu PH, Thuille B et al (1997) BAT-26, an indicator of the replication error phenotype in colorectal cancers and cell lines. Cancer Res 57:300–303PubMedGoogle Scholar
  9. 9.
    Cravo M, Lage P, Albuquerque C et al (1999) BAT-26 identifies sporadic colorectal cancers with mutator phenotype: a correlative study with clinico-pathological features and mutations in mismatch repair genes. J Pathol 188:252–257PubMedCrossRefGoogle Scholar
  10. 10.
    Dietmaier W, Wallinger S, Bocker T et al (1997) Diagnostic microsatellite instability: definition and correlation with mismatch repair protein expression. Cancer Res 57:4749–4756PubMedGoogle Scholar
  11. 11.
    Sutter C, Gebert J, Bischoff P et al (1999) Molecular screening of potential HNPCC patients using a multiplex microsatellite PCR system. Mol Cell Probe 13:157–165CrossRefGoogle Scholar
  12. 12.
    Loukola A, Vilkki S, Singh J et al (2000) Germline and somatic mutation analysis of MLH3 in MSI-positive colorectal cancer. Am J Pathol 157:347–352PubMedCrossRefGoogle Scholar
  13. 13.
    Perucho M Correspondence Re: C.R. Boland et al (1999) 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., 58:5248–5257, 1988. Cancer Res 59:249–256Google Scholar
  14. 14.
    Boland R, Goel A (2010) Microsatellite instability in colorectal cancer. Gastroenterology 138:2073–2087PubMedCrossRefGoogle Scholar
  15. 15.
    Loukola A, Eklin K, Laiho P et al (2001) Microsatellite marker analysis in screening for hereditary nonpolyposis colorectal cancer (HNPCC). Cancer Res 61:4545–4549PubMedGoogle Scholar
  16. 16.
    Park JW, Chang HJ, Jung KH et al (2008) Clinicopathologic features of sporadic colorectal cancer with MLH1/MSH2 loss of expression—reduced likelihood of metastases. J Korean Soc Coloproctol 24:175–183CrossRefGoogle Scholar
  17. 17.
    Chapusot C, Martin L, Mungra N et al (2003) Sporadic colorectal cancers with defective mismatch repair display a number of specific morphological characteristics: relationship between the expression of hMLH1 and hMSH2 proteins and clinicopathological features of 273 adenocarcinomas. Histopathology 43:40–47PubMedCrossRefGoogle Scholar
  18. 18.
    Park JG, Vasen HF, Park YJ et al (2001) Suspected HNPCC and Amsterdam criteria II: evaluation of mutation detection rate, an international collaborative study. Int J Colorectal Dis 17:109–114CrossRefGoogle Scholar
  19. 19.
    Hampel H, Frankel WL, Martin E et al (2005) Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med 352:1851–1860PubMedCrossRefGoogle Scholar
  20. 20.
    Rusin LC, Galandiuk S (2007) Hereditary nonpolyposis colorectal cancer. In: Wolff BG, Fleshman JW, Beck DE (eds) The ASCRS textbook of colon and rectal surgery. Springer, New York, pp 525–542CrossRefGoogle Scholar
  21. 21.
    Schwartz RA, Torre DP (1995) The muir-torre syndrome: 25 year retrospective. J Am Acad Dermatol 33:90–104PubMedCrossRefGoogle Scholar
  22. 22.
    Rodriguez-Bigas M, Boland CR, Hamilton SR et al (1997) A national cancer institute workshop on HNPCC: meeting highlights and Bethesda guidelines. J Natl Cancer Inst 89:1758–1762PubMedCrossRefGoogle Scholar
  23. 23.
    Thibodeau SN, French AJ, Cunningham JM et al (1998) Microsatellite instability in colorectal cancer: different mutator phenotypes and the principal involvement of hMLH1. Cancer Res 58:1713–1718PubMedGoogle Scholar
  24. 24.
    Vasen HFA, Moeslein G, Alonso A et al (2010) Recommendations to improve identification of hereditary and familial colorectal cancer in Europe. Fam Cancer 9:109–115PubMedCrossRefGoogle Scholar
  25. 25.
    Jass JR (2004) HNPCC and sporadic MSI-H colorectal cancer: a review of the morphological similarities and differences. Fam Cancer 3:93–100PubMedCrossRefGoogle Scholar
  26. 26.
    Popat S, Hubner R, Houlston RS (2005) Systematic review of micro-satellite instability and colorectal cancer prognosis. J Clin Oncol 23:609–618PubMedCrossRefGoogle Scholar
  27. 27.
    Lanza G, Gafa R, Santini A et al (2006) Immunohistochemical test for MLH1 and MSH2 expression predicts clinical outcome in stage II and III colorectal cancer patients. J Clin Oncol 24:2359–2367PubMedCrossRefGoogle Scholar
  28. 28.
    Samowitz WS, Curtin K, Ma KN et al (2001) Microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level. Cancer Epidemiol Biomarkers Prev 10:917–923PubMedGoogle Scholar
  29. 29.
    Phillips SM, Banerjea A, Feakins R et al (2004) Tumour-infiltrating lymphocytes in colorectal cancer with microsatellite instability are activated and cytotoxic. Br J Surg 91:469–475PubMedCrossRefGoogle Scholar
  30. 30.
    Galon J, Costes A, Sanchez-Cabo F et al (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313:1960–1964PubMedCrossRefGoogle Scholar
  31. 31.
    Agostini M, Enzo MV, Morandi L et al (2010) A ten markers panel provides a more accurate and complete microsatellite instability analysis in mismatch repair-deficient colorectal tumors. Cancer Biomark 6:49–61PubMedGoogle Scholar
  32. 32.
    Zhang L (2008) Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome: the utility of microsatellite instability testing. J Mol Diagn 10:301–307PubMedCrossRefGoogle Scholar
  33. 33.
    Suraweera N, Duval A, Reperant M et al (2002) Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR. Gastroenterology 123:1804–1811PubMedCrossRefGoogle Scholar
  34. 34.
    Laghi L, Bianchi P, Malesci A (2008) Differences and evolution of the methods for the assessment of microsatellite instability. Oncogene 27:6313–6321PubMedCrossRefGoogle Scholar
  35. 35.
    Jass JR, Biden KG, Cummings MC et al (1999) Characterisation of a subtype of colorectal cancer combining features of the suppressor and mild mutator pathways. J Clin Pathol 52:455–460PubMedCrossRefGoogle Scholar
  36. 36.
    Mori Y, Selaru FM, Sato F et al (2003) The impact of microsatellite instability on the molecular phenotype of colorectal tumors. Cancer Res 63:4577–4582PubMedGoogle Scholar
  37. 37.
    Oliart S, Martinez-Santos C, Moreno-Azcoita M et al (2006) Do MSI-L sporadic colorectal tumors develop through “mildmutatorpathway”? Am J Clin Oncol 29:364–370PubMedCrossRefGoogle Scholar
  38. 38.
    Halling KC, French AJ, McDonnell SK et al (1999) Microsatellite instability and 8p allelic imbalance in stage B2 and C colorectal cancers. J Natl Cancer Inst 91:1295–1303PubMedCrossRefGoogle Scholar
  39. 39.
    Kohonen-Corish MR, Daniel JJ, Chan C et al (2005) Low microsatellite instability is associated with poor prognosis in stage C colon cancer. J Clin Oncol 23:2318–2324PubMedCrossRefGoogle Scholar
  40. 40.
    Wright CM, Dent OF, Newland RC et al (2005) Low level microsatellite instability may be associated with reduced cancer specific survival in sporadic stage C colorectal carcinoma. Gut 54:103–108PubMedCrossRefGoogle Scholar
  41. 41.
    Asaka S, Arai Y, Nishimura Y et al (2009) Microsatellite instability-low colorectal cancer acquires a KRAS mutation during the progression from Dukes’ A to Dukes’ B. Carcinogenesis 30:494–499PubMedCrossRefGoogle Scholar
  42. 42.
    Yamada K, Kanazawa S, Koike J et al (2010) Microsatellite instability at tetranucleotide repeats in sporadic colorectal cancer in Japan. Oncol Rep 23:551–561PubMedCrossRefGoogle Scholar
  43. 43.
    Hatch SB, Lightfoot HM, Garwacki CP et al (2005) Microsatellite instability testing in colorectal carcinoma: choice of markers affects sensitivity of detection of mismatch repair-deficient tumors. Clin Cancer Res 11:2180–2187PubMedCrossRefGoogle Scholar
  44. 44.
    Meng WJ, Sun XF, Tian C et al (2007) Microsatellite instability did not predict individual survival in sporadic stage II and III rectal cancer patients. Oncology 72:82–88PubMedCrossRefGoogle Scholar
  45. 45.
    Huang YQ, Yuan Y, Ge WT et al (2010) Comparative features of colorectal and gastric cancers with microsatellite instability in Chinese patients. J Zhejiang Univ Sci B 11:647–653PubMedCrossRefGoogle Scholar
  46. 46.
    Vilkin A, Niv Y, Nagaska T et al (2009) Microsatellite instability, MLH1 promoter methylation, and BRAF mutation analysis in sporadic colorectal cancers of different ethnic groups in Israel. Cancer 115:760–769PubMedCrossRefGoogle Scholar
  47. 47.
    Kim GP, Colangelo LH, Wieand HS et al (2007) Prognostic and predictive roles of high-degree microsatellite instability in colon cancer: a national cancer institute-national surgical adjuvant breast and bowel project collaborative study. J Clin Oncol 25:767–772PubMedCrossRefGoogle Scholar
  48. 48.
    Gryfe R, Kim H, Hsieh ET et al (2000) Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med 342:69–77PubMedCrossRefGoogle Scholar
  49. 49.
    Ashktorab H, Smoot DT, Farzanmehr H et al (2005) Clinicopathological features and microsatellite instability (MSI) in colorectal cancers from African Americans. Int J Cancer 116:914–919PubMedCrossRefGoogle Scholar
  50. 50.
    Vasovcak P, Pavlikova K, Sedlacek Z et al (2011) Molecular genetic analysis of 103 sporadic colorectal tumours in Czech patients. PLoS One 6:e24114PubMedCrossRefGoogle Scholar
  51. 51.
    Nakayama K, Bayasgalan T, Tazoe F et al (2010) A single nucleotide polymorphism in the FADS1/FADS2 gene is associated with plasma lipid profiles in two genetically similar Asian ethnic groups with distinctive differences in lifestyle. Hum Genet 127:685–690PubMedCrossRefGoogle Scholar
  52. 52.
    Tunca B, Pedroni M, Cecener G et al (2010) Analysis of mismatch repair gene mutations in Turkish HNPCC patients. Fam Cancer 9:365–376PubMedCrossRefGoogle Scholar
  53. 53.
    De Jesus-Monge WE, Gonzalez-Keelan C, Zhao R et al (2010) Mismatch repair protein expression and colorectal cancer in hispanics from Puerto Rico. Fam Cancer 9:155–166PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Jung Ryul Oh
    • 1
  • Duck-Woo Kim
    • 1
    • 2
    Email author
  • Hye Seung Lee
    • 3
  • Hee Eun Lee
    • 3
  • Sung Min Lee
    • 1
  • Je-Ho Jang
    • 1
  • Sung-Bum Kang
    • 1
  • Ja-Lok Ku
    • 2
  • Seung-Yong Jeong
    • 2
  • Jae-Gahb Park
    • 2
  1. 1.Department of SurgerySeoul National University Bundang HospitalSeongnamKorea
  2. 2.Korean Hereditary Tumor Registry, Cancer Research InstituteSeoul National University College of MedicineSeoulKorea
  3. 3.Department of PathologySeoul National University Bundang HospitalSeongnamKorea

Personalised recommendations