Skip to main content

Advertisement

Log in

Microsatellite instability screening should be done for right-sided colon cancer patients less than 60 years of age

  • Original Article
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background and aims

Microsatellite analysis is a screening tool used for the identification of Lynch syndrome. We evaluated the occurrence of high-frequency microsatellite instability (MSI-H) in 160 patients with colorectal cancer ≤60 years old to determine if these individuals should be routinely tested for microsatellite instability.

Materials and methods

From January 2004 and December 2006, we tested specimens of colorectal cancer from 160 patients under 60 years of age for microsatellite instability. The relationships between clinicopathological parameters and MSI-H status were analyzed.

Results

MSI-H occurred in 11.3% (18/160) of the tumors assayed, and colorectal tumors with MSI-H status were located predominantly to the right side (56%, P < 0.001) and had a lower pathological stage (72%, P = 0.011). Of the 18 MSI-H tumors, six displayed characteristic MSI histology. Furthermore, of the 18 MSI-H tumors, instability in BAT-26 was 100%, BAT-25 was 94%, D17S250 was 72%, D2S123 was 68%, and D5S346 was 68%. Of the patients with MSI-H tumors, 55.6% were more than 50 years of age, and about 70% of MSI-H tumors did not display characteristic MSI histology. Importantly, up to 40% of the MSI-H patients in this study would have been overlooked using the revised Bethesda guidelines. The revised Bethesda guidelines, broadened to include patients with right-sided colon cancer, could have identified 94% of the MSI-H tumors in this study.

Conclusions

Colorectal cancers with MSI-H were predominantly located on the right side and had an early pathological stage. The results of this study suggest that microsatellite instability test should be used for all patients under 60 years of age with right-sided colon cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

CRC:

Colorectal cancer

MSI:

Microsatellite instability

MMR:

Mismatch repair

References

  1. Lee ML (1998) Cancer incidence in Taiwan. Department of Health, Taipei

    Google Scholar 

  2. Lengauer C, Kinzler KW, Vogelstein B (1998) Genetic instabilities in human cancers. Nature 396:643–649

    Article  CAS  PubMed  Google Scholar 

  3. Lothe RA, Peltomaki P, Meling GI et al (1993) Genomic instability in colorectal cancer: relationship to clinicopathological variables and family history. Cancer Res 53:5849–5852

    CAS  PubMed  Google Scholar 

  4. Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL (1988) Genetic alterations during colorectal tumor development. N Engl J Med 319:525–532

    CAS  PubMed  Google Scholar 

  5. Vogelstein B, Fearon ER, Kern SE, Hamilton SR, Preisinger AC, Nakamura Y, White R (1989) Allelotype of colorectal carcinomas. Science 244:207–211

    Article  CAS  PubMed  Google Scholar 

  6. Lengauer C, Kinzler KW, Vogelstein B (1997) DNA methylation and genetic instability in colorectal cancer cells. Proc Natl Acad Sci USA 94:2545–2550

    Article  CAS  PubMed  Google Scholar 

  7. Kinzler KW, Vogelstein B (1996) Lessons from hereditary colorectal cancer. Cell 87:159–170

    Article  CAS  PubMed  Google Scholar 

  8. Gryfe R, Kim H, Hsieh ET, Aronson MD, Holowaty EJ, Bull SB, Redston M, Gallinger S (2000) Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med 342:69–77

    Article  CAS  PubMed  Google Scholar 

  9. Strand M, Prolla TA, Liskay RM, Petes TD (1993) Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature 365:274–276

    Article  CAS  PubMed  Google Scholar 

  10. Leach FS, Nicolaides NC, Papadopoulos N et al (1993) Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 75:1215–1225

    Article  CAS  PubMed  Google Scholar 

  11. Fishel R, Lescoe MK, Rao MR et al (1993) The human mutator gene homologue MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 75:1027–1038

    Article  CAS  PubMed  Google Scholar 

  12. Papadopoulos N, Nicolaides NC, Wei YF et al (1994) Mutation of a mutL homolog in hereditary colon cancer. Science 263:1625–1629

    Article  CAS  PubMed  Google Scholar 

  13. Bronner CE, Baker SM, Morrison PT et al (1994) Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature 368:258–261

    Article  CAS  PubMed  Google Scholar 

  14. Cunningham JM, Christensen ER, Tester DJ, Kim CY, Roche PC, Burgart LJ, Thibodeau SN (1998) Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res 58:3455–3460

    CAS  PubMed  Google Scholar 

  15. Mangold E, Pagenstecher C, Friedl W et al (2005) Spectrum and frequencies of mutations in MSH2 and MLH1 identified in 1721 German families suspected of hereditary nonpolyposis colorectal cancer. Int J Cancer 116:692–702

    Article  CAS  PubMed  Google Scholar 

  16. Aaltonen LA, Peltomaki P, Mecklin J-P et al (1994) Replication errors in benign and malignant tumors from hereditary nonpolyposis colorectal cancer patients. Cancer Res 54:1645–1648

    CAS  PubMed  Google Scholar 

  17. Thibodeau SN, Bren G, Schaid D (1993) Microsatellite instability in cancer of the proximal colon. Science 260:816–819

    Article  CAS  PubMed  Google Scholar 

  18. 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 363:558–561

    Article  CAS  PubMed  Google Scholar 

  19. Aaltonen LA, Salovaara R, Kristo P et al (1998) Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med 338:1481–1487

    Article  CAS  PubMed  Google Scholar 

  20. Vasen HFA, Möslein G, Alonso A et al (2007) Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer). J Med Genet 44:353–362

    Article  CAS  PubMed  Google Scholar 

  21. Umar A, Boland CR, Terdiman JP et al (2004) Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. Natl Cancer Inst 96:261–268

    CAS  Google Scholar 

  22. Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Nakagawa H, Sotamaa K, Prior TW, Westman J, Panescu J, Fix D, Lockman J, Comeras I, de la Chapelle A (2005) Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med 352:1851–1860

    Article  CAS  PubMed  Google Scholar 

  23. 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 58:5248–5257

    CAS  PubMed  Google Scholar 

  24. Hamilton SR, Aaltonen LA (2000) World Health Organization classification of tumours. Pathology and genetics of tumours of the digestive system. IARC Press, Lyon

    Google Scholar 

  25. Lynch HT, de la Chapelle A (1999) Genetic susceptibility to non-polyposis colorectal cancer. J Med Genet 36:801–818

    CAS  PubMed  Google Scholar 

  26. Jass JR, Stewart SM (1992) Evolution of hereditary non-polyposis colorectal cancer. Gut 33:783–786

    Article  CAS  PubMed  Google Scholar 

  27. Mecklin J-P, Sipponen P, Jarvinen HJ (1986) Histopathology of colorectal carcinomas and adenomas in cancer family syndrome. Dis Colon Rectum 29:849–853

    Article  CAS  PubMed  Google Scholar 

  28. Jass JR, Cottier DS, Jeevaratnam P, Pokos V, Browett P (1996) Pathology of hereditary non-polyposis colorectal cancer with clinical and molecular genetic correlations. In: Baba S (ed) New strategies for treatment of hereditary colorectal cancer. Churchill Livingstone, Tokyo, Japan

    Google Scholar 

  29. Kim H, Jen J, Vogelstein B, Hamilton SR (1994) Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences. Am J Pathol 145:148–156

    CAS  PubMed  Google Scholar 

  30. Jass JR, Do K-A, Simms LA, Iino H, Wynter C, Pillay SP, Searle J, Radford-Smith G, Young J, Leggett B (1998) Morphology of sporadic colorectal cancer with DNA replication errors. Gut 42:673–679

    Article  CAS  PubMed  Google Scholar 

  31. Alexander J, Watanabe T, Tsung-Teh W, Rashid A, Li S, Hamilton SR (2001) Histopathological identification of colon cancer with microsatellite instability. Am J Pathol 158:527–535

    CAS  PubMed  Google Scholar 

  32. Gafa R, Maestri I, Matteuzzi M, Santini A, Ferretti S, Cavazzini L, Lanza G (2000) Sporadic colorectal adenocarcinomas with high-frequency microsatellite instability. Cancer 89:2025–2037

    Article  CAS  PubMed  Google Scholar 

  33. Ward R, Meagher A, Tomlinson I, O’Connor T, Norrie M, Wu R, Hawkins N (2001) Microsatellite instability and the clinicopathological features of sporadic colorectal cancer. Gut 48:821–829

    Article  CAS  PubMed  Google Scholar 

  34. Graham DM, Appelman HD (1990) Crohn's-like lymphoid reaction and colorectal carcinoma: a potential histologic prognosticator. Mod Pathol 3:332–335

    CAS  PubMed  Google Scholar 

  35. Greenson JK, Bonner JD, Ben-Yzhak O, Cohen HI, Miselevich I, Resnick MB, Trougouboff P, Tomsho LD, Kim E, Low M, Almog R, Rennert G, Gruber SB (2003) Phenotype of microsatellite unstable colorectal carcinomas. Am J Surg Pathol 27:563–570

    Article  PubMed  Google Scholar 

  36. Smyrk TC, Watson P, Kaul K, Lynch HT (2001) Tumor-infiltrating lymphocytes are a marker for microsatellite instability in colorectal cancer. Cancer 91:2417–2422

    Article  CAS  PubMed  Google Scholar 

  37. Jenkins MA, Hayashi S, O'Shea AM et al (2007) Pathology features in Bethesda guidelines predict colorectal cancer microsatellite Instability: a population-based study. Gastroenterology 133:48–56

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shin-Ching Chang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chou, CL., Lin, JK., Wang, HS. et al. Microsatellite instability screening should be done for right-sided colon cancer patients less than 60 years of age. Int J Colorectal Dis 25, 47–52 (2010). https://doi.org/10.1007/s00384-009-0815-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-009-0815-y

Keywords

Navigation