Molecular Biology Reports

, Volume 37, Issue 1, pp 375–380 | Cite as

Assessment of microsatellite instability in colorectal cancer patients from Brazil

  • Sinara M. O. Leite
  • Karina B. Gomes
  • Victor C. Pardini
  • Alessandro C. S. Ferreira
  • Vanessa C. Oliveira
  • Geraldo M. G. Cruz
Article

Abstract

The replication error status analysis of DNA, through microsatellite instability detection, has become an indispensable tool for hereditary non-polyposis colorectal cancer screening. This study investigated the microsatellite instability in Brazilian individuals presenting colorectal cancer. In this study, 66 patients were clinically analyzed according to Amsterdam II and Bethesda guidelines. Normal and tumour tissues were collected and analyzed for MSI degree according to molecular markers BAT25, BAT26, BAT40, APC–D5S346, D2S123, and D17S250. Eight patients (12.1%) fulfilled the Amsterdam II guidelines, and 15 (22.7%) met the Bethesda guidelines. BAT25 was the most sensitive marker (86.7%), while BAT26 was the least sensitive (66.7%). The specificity of both markers was 100%, but all of the markers must be used since the contribution of each marker to the sensitivity and specificity of the test is complementary. Proximal tumours were significantly predominant among RER+ patients. Conclusions: Patients with a family history of colorectal cancer with the tumour in the proximal colon must be screened to replication error status as early as possible in order to avoid the progression of the disease.

Keywords

Amsterdam II Bethesda Colorectal cancer Microsatellite instability Replication error status 

References

  1. 1.
    Rossi B, Nakagawa W, Ferreira F, Aguiar JS, Lopes A (2004) Câncer de cólon, reto e ânus, 1st edn. Lemar e Tecmedd, São PauloGoogle Scholar
  2. 2.
    Lynch H, De La Chapelle A (2003) Hereditary colorectal cancer. N Engl J Med 348:919–932CrossRefPubMedGoogle Scholar
  3. 3.
    Fearon E, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767CrossRefPubMedGoogle Scholar
  4. 4.
    Aaltonen L, Peltomäki P, Leach F, Sistonen P, Pylkkänen L, Mecklin J et al (1993) Clues to the pathogenesis of familial colorectal cancer. Science 260:812–816CrossRefPubMedGoogle Scholar
  5. 5.
    Thibodeau S, Bren G, Schaid D (1993) Microsatellite instability in cancer of the proximal colon. Science 260:816–819CrossRefPubMedGoogle Scholar
  6. 6.
    Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M (1993) Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 363:558–561CrossRefPubMedGoogle Scholar
  7. 7.
    Papadopoulos N, Nicolaides NC, Wei YF, Ruben SM, Carter KC, Rosen CA et al (1994) Mutation of a mutL homolog in hereditary colon cancer. Science 262:1625–1629CrossRefGoogle Scholar
  8. 8.
    Wheeler JM, Bodmer WF, Mortensen NJ (2000) DNA mismatch repair genes and colorectal cancer. Gut 47:148–153CrossRefPubMedGoogle Scholar
  9. 9.
    Jass JR (1999) Towards a molecular classification of colorectal cancer. Int J Colorectal Dis 14:194–200CrossRefPubMedGoogle Scholar
  10. 10.
    Bronner CE, Baker SM, Morrison PT, Warren G, Smith LG, Lescoe MK et al (1994) Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature 368:258–261CrossRefPubMedGoogle Scholar
  11. 11.
    Thibodeau SN, French AJ, Cunningham JM, Tester D, Burgart LJ, Roche PC et al (1998) Microsatellite instability in colorectal cancer: different mutator phenotypes and the principal involvement of hMLH1. Cancer Res 58:1713–1718PubMedGoogle Scholar
  12. 12.
    Cunningham JM, Christensen ER, Tester DJ, Kim CY, Roche PC, Burgart LJ et al (1998) Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res 58:3455–3460PubMedGoogle Scholar
  13. 13.
    Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Rüschoff J et al (2004) Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96:261–268PubMedCrossRefGoogle Scholar
  14. 14.
    Zhang L (2008) Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part II. The utility of microsatellite instability testing. J Mol Diagn 10:301–307CrossRefPubMedGoogle Scholar
  15. 15.
    Giráldez MD, Castellví-Bel S, Balaguer F, Gonzalo V, Ocaña T, Castells A (2008) Lynch syndrome in colorectal cancer patients. Expert Rev Anticancer Ther 8:573–583CrossRefPubMedGoogle Scholar
  16. 16.
    Mullis K, Faloona F (1987) Specific synthesis of DNA in vitro via polymerase-catalyzed chain reaction. Methods Enzymol 155:335–350CrossRefPubMedGoogle Scholar
  17. 17.
    Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT et al (1988) Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:487–491CrossRefPubMedGoogle Scholar
  18. 18.
    Gryfe R, Kim H, Hsieh ET, Aronson MD, Holowaty EJ, Bull SB et al (2000) Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med 342:69–77CrossRefPubMedGoogle Scholar
  19. 19.
    Wright CM, Dent OF, Barker M, Newland RC, Chapuis PH, Bokey EL et al (2000) Prognostic significance of extensive microsatellite instability in sporadic clinicopathological stage C colorectal cancer. Br J Surg 87:1197–1202CrossRefPubMedGoogle Scholar
  20. 20.
    Hamelin R, Chalastanis A, Colas C, El Bchiri J, Mercier D et al (2008) Clinical and molecular consequences of microsatellite instability in human cancers. Bull Cancer 95:121–132PubMedGoogle Scholar
  21. 21.
    Hemminki A, Mecklin JP, Järvinen H, Aaltonen LA, Joensuu H (2000) Microsatellite instability is a favourable prognostic indicator in patients with colorectal cancer receiving chemotherapy. Gastroenterology 119:921–928CrossRefPubMedGoogle Scholar
  22. 22.
    Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM et al (2003) Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 349:247–257CrossRefPubMedGoogle Scholar
  23. 23.
    Bouzourene H, Taminelli L, Chaubert P, Monnerat C, Seelentag W, Sandmeier D et al (2006) A cost-effective algorithm for hereditary non-polyposis colorectal cancer detection. Am J Clin Pathol 125(6):823–831CrossRefPubMedGoogle Scholar
  24. 24.
    Manne SL, Chung DC, Weinberg DS, Vig HS, Catts Z, Cabral MK et al (2007) Knowledge and attitudes about microsatellite instability testing among high-risk individuals diagnosed with colorectal cancer. Cancer Epidemiol Biomarkers Prev 16:2110–2117CrossRefPubMedGoogle Scholar
  25. 25.
    Syngal S, Fox EA, Eng C, Kolodner RD, Garber JE (2000) Sensitivity and specificity of clinical criteria for hereditary non-polyposis colorectal cancer associated mutations in MSH2 and MLH1. J Med Genet 37:641–645CrossRefPubMedGoogle Scholar
  26. 26.
    Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P et al (2005) Screening for the Lynch syndrome (hereditary non-polyposis colorectal cancer). N Engl J Med 352:1851–1860CrossRefPubMedGoogle Scholar
  27. 27.
    De La Chapelle A (2002) Microsatellite instability phenotype of tumors: genotyping or immunohistochemistry? The jury is still out (Editorial). J Clin Oncol 20:897–899PubMedGoogle Scholar
  28. 28.
    De La Chapelle A (2005) The incidence of Lynch syndrome. Fam Cancer 4:233–237CrossRefGoogle Scholar
  29. 29.
    Wakefield CE, Meiser B, Homewood J, Ward R, O’Donnell S, Kirk J et al. (2008) Randomized trial of a decision aid for individuals considering genetic testing for hereditary nonpolyposis colorectal cancer risk. Cancer, 10 JulyGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Sinara M. O. Leite
    • 1
    • 4
  • Karina B. Gomes
    • 2
  • Victor C. Pardini
    • 3
  • Alessandro C. S. Ferreira
    • 3
  • Vanessa C. Oliveira
    • 3
  • Geraldo M. G. Cruz
    • 1
  1. 1.Department of ColoproctologySanta Casa de Belo HorizonteBrazil
  2. 2.COLTEC, Federal University of Minas GeraisBelo HorizonteBrazil
  3. 3.Department of Human GeneticsInstituto H. PardiniBelo HorizonteBrazil
  4. 4.Serra Belo HorizonteBrazil

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