Medical Oncology

, Volume 29, Issue 3, pp 1796–1801

Microsatellite instability in metastatic colorectal cancer: a review of pathology, response to chemotherapy and clinical outcome

Review Article

Abstract

Approximately 10% of colorectal carcinomas demonstrate microsatellite instability (MSI). Distinct from the majority of colorectal cancers with chromosomal instability (CIN) which harbour allelic imbalance from chromosomal polyploidy and aneuploidy, MSI tumours retain intact chromosomal numbers but contain microsatellite repeats due to deficiency in mismatch repair which are thought to contribute to the early steps of tumourigenesis in colorectal cancer. While emerging clinical data has highlighted improved prognosis of tumours with MSI in early colorectal cancer and potentially circumventing the need for adjuvant chemotherapy, the implications of MSI deficiency in metastatic colorectal cancer (mCRC) remain uncertain. In order to assess the significance of MSI in mCRC, a broad literature review was carried out through online PubMed search on published articles encompassing pathological and clinical papers. This included pathological studies identifying the correlation with MSI status between primary sites and metastases, and chemotherapeutic studies assessing the impact of fluoropyrimidine-, irinotecan- and oxaliplatin-based regimens on mCRC with MSI.

Keywords

Advanced Chemotherapy Colorectal Instability Metastatic Microsatellite 

References

  1. 1.
    Gryfe R, Kim H, Hsieh ET, et al. Tumour microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med. 2000;342:69–77.PubMedCrossRefGoogle Scholar
  2. 2.
    Schneider A, Rohr S, Kelly MD, et al. Microsatellite instability and allelic imbalance in primary and secondary colorectal cancer. Aust NZ J Surg. 2000;70:587–92.CrossRefGoogle Scholar
  3. 3.
    Wheeler JM, Beck NE, Kim HC, et al. Mechanisms of inactivation of mismatch repair genes in human colorectal cancer cell lines: the predominant role of hMLH1. Proc Natl Acad Sci USA. 1999;96:10296–301.PubMedCrossRefGoogle Scholar
  4. 4.
    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;58:5248–57.Google Scholar
  5. 5.
    Rosty C, Chazal M, Etienne MC, et al. Determination of microsatellite instability, p53 and K-RAS mutations in hepatic metastases from patients with colorectal cancer: relationship with response to 5-fluorouracil and survival. Int J Cancer. 2001;95:162–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Mead LJ, Jenkins MA, Young J, et al. Microsatellite instability markers for identifying early-onset colorectal cancers caused by germ-line mutations in DNA mismatch repair genes. Clin Cancer Res. 2007;13:2865–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Ishimaru G, Adachi J, Shiseki M, et al. Microsatellite instability in primary and metastatic colorectal cancers. Int J Cancer. 1995;64:153–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Ding SF, Delhanty JD, Zografos G, et al. Chromosome allele loss in colorectal liver metastases and its association with clinical features. Br J Surg. 1994;81:875–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science. 1993;260:816–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Kochhar R, Halling KC, McDonnell S, et al. Allelic imbalance and microsatellite instability in resected Duke’s D colorectal cancer. Diagn Mol Pathol. 1997;6:78–84.PubMedCrossRefGoogle Scholar
  11. 11.
    Chen WS, Chen JY, Liu JM, et al. Microsatellite instability in sporadiccolon- cancer patients with and without liver metastases. Int J Cancer. 1997;74:470–4.PubMedCrossRefGoogle Scholar
  12. 12.
    Haddad R, Ogilvie RT, Croitoru M, et al. Microsatellite instability as a prognostic factor in resected colorectal cancer liver metastases. Ann Surg Oncol. 2004;11:977–82.PubMedCrossRefGoogle Scholar
  13. 13.
    Liang JT, Huang KC, Lai HS, et al. High-frequency microsatellite instability predicts better chemosensitivity to high-dose 5-fluorouracil plus leucovorin chemotherapy for stage IV sporadic colorectal cancer after palliative bowel resection. Int J Cancer. 2002;101:519–25.PubMedCrossRefGoogle Scholar
  14. 14.
    Brueckl WM, Moesch C, Brabletz T, et al. Relationship between microsatellite instability, response and survival in palliative patients with colorectal cancer undergoing first-line chemotherapy. Anticancer Res. 2003;23:1773–7.PubMedGoogle Scholar
  15. 15.
    Fallik D, Borrini F, Boige V, et al. Microsatellite instability is a predictive factor of the tumour response to irinotecan in patients with advanced colorectal cancer. Cancer Res. 2003;63:5738–44.PubMedGoogle Scholar
  16. 16.
    Des GuetzG, Mariani P, Cucherousset J, et al. Microsatellite instability and sensitivitiy to FOLFOX treatment in metastatic colorectal cancer. Anticancer Res. 2001;27:2715–9.Google Scholar
  17. 17.
    Muller CI, Schulmann K, Reinacher-Schick A et al. Predictive and prognostic value of microsatellite instability in patients with advanced colorectal cancer treated with a fluoropyrimidine and oxaliplatin containing first-line chemotherapy. A report of the AIO Colorectal Study Group. Int J Colorectal Dis. 2008;23:1033–39.Google Scholar
  18. 18.
    Koopman M, Kortman GA, Mekenkamp L, et al. Deficient mismatch repair system in patients with sporadic advanced colorectal cancer. Br J Cancer. 2009;27:266–73.CrossRefGoogle Scholar
  19. 19.
    Des Guetz G, Uzzan B, Nicolas P, et al. Microsatellite instability does not predict the efficacy of chemotherapy in metastatic colorectal cancer. A systematic review and meta-analysis. Anticancer Res. 2009;29:1615–20.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Gastrointestinal Cancer and Lymphoma Research UnitThe Royal Marsden NHS Foundation TrustLondon and SurreyUnited Kingdom

Personalised recommendations