Skip to main content
SpringerLink
Log in

Microsatellite instability: a predictive marker in metastatic colorectal cancer?

  • Original Research
  • Published:
Targeted Oncology Aims and scope Submit manuscript

Abstract

Microsatellite instability (MSI) status is a good prognostic factor for colorectal cancer (CRC), but its predictive value for chemosensitivity remains controversial. We recently performed a meta-analysis (MA) in adjuvant setting showing that MSI high (MSI-H) status did not predict the efficacy of chemotherapy. Studies were identified by electronic search through PubMed, Embase and ASCO proceedings online databases, using several keywords (colorectal cancer, chemotherapy, microsatellite instability). For each study, we calculated the ratio of response rate, complete and partial responses divided by stable disease and progression. Our MA dealt with the predictive value of MSI status on the effect of metastatic chemotherapy using various combinations of 5FU, oxaliplatin or CPT11. From 159 articles and 76 abstracts, we selected only seven independent studies. Data were analysed with a random-effect model (due to heterogeneity between studies) using EasyMA software. Statistical calculations were performed on five studies representing 860 patients (mean age 63 years; 87 MSI-H; 733 microsatellite stable [MSS] tumors). A total of 287 patients received 5FU-based chemotherapy, whereas 574 patients received combinations of 5FU or capecitabine with oxaliplatin and/or irinotecan. Our MA found no benefit of metastatic chemotherapy in terms of response rate for MSI-H patients compared with MSS patients. The global hazard ratio for response rate was 0.83 (95% confidence interval: 0.95; 0.65–1.05; p = 0.11). In conclusion, MSI status did not predict the effect of chemotherapy for metastatic CRC. Metastatic chemotherapy had a similar effect on both MSI-H or on MSS tumors.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Weitz J, Koch M, Debus J, Hohler T, Galle PR, Buchler MW (2005) Colorectal cancer. Lancet 365:153–165

    Article  PubMed  Google Scholar 

  2. Duval A, Hamelin R (2002) Mutations at coding repeat sequences in mismatch repair-deficient human cancers: Toward a new concept of target genes for instability. Cancer Res 62:2447–2454

    CAS  PubMed  Google Scholar 

  3. Popat S, Hubner R, Houlston RS (2005) Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol 23:609–618

    Article  CAS  PubMed  Google Scholar 

  4. Umar A, Boland CR, Terdiman JP, Syngal S, Chapelle ADL, Ruschoff J et al (2004) Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch Syndrome) and microsatellite instability. J Natl Cancer Inst 96:261–268

    Article  CAS  PubMed  Google Scholar 

  5. Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW 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 

  6. Buhard O, Cattaneo F, Wong YF, Yim SF, Friedman E, Flejou J-F et al (2006) Multipopulation analysis of polymorphisms in five mononucleotide repeats used to determine the microsatellite instability status of human tumors. J Clin Oncol 24:241–251

    Article  CAS  PubMed  Google Scholar 

  7. Altman DG (2001) Systematic reviews in health care: Systematic reviews of evaluations of prognostic variables. BMJ 323:224–228

    Article  CAS  PubMed  Google Scholar 

  8. Fallik D, Borrini F, Boige V, Viguier J, Jacob S, Miquel C et al (2003) Microsatellite instability is a predictive factor of the tumor response to irinotecan in patients with advanced colorectal cancer. Cancer Res 63:5738–5744

    CAS  PubMed  Google Scholar 

  9. Brueckl WM, Moesch C, Brabletz T, Koebnick C, Riedel C, Jung A et al (2003) Relationship between microsatellite instability, response and survival in palliative patients with colorectal cancer undergoing first-line chemotherapy. Anticancer Res 23:1773–1777

    CAS  PubMed  Google Scholar 

  10. Jin-Tung L, Kou-Chin H, Hong-Shiee L, Po-Huang L, Yung-Ming C, Hey-Chi H, Ann-Lii C, Chih-Hung H, Kun-Huei Y, Shih-Ming W, Chi T, King-Jen (2002) 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. International Journal of Cancer 101:519–525

    Article  CAS  Google Scholar 

  11. Rosty C, Chazal M, Etienne MC, Letoublon C, Bourgeon A, Delpero JR et al (2001) 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 95:162–167

    Article  CAS  PubMed  Google Scholar 

  12. des Guetz G, Mariani P, Cucherousseto J, Benamoun M, Lagorce C, Sastre X et al (2007) Microsatellite instability and sensitivity to FOLFOX treatment in metastatic colorectal cancer. Anticancer Res 27:2715–2719

    CAS  PubMed  Google Scholar 

  13. Bendardaf R, Lamlum H, Ristamaki R, Korkeila E, Syrjanen K, Pyrhonen S (2007) Mismatch repair status is a predictive factor of tumour response to 5-fluorouracil and irinotecan chemotherapy in patients with advanced colorectal cancer. Tumour Biol 28:212–220

    Article  CAS  PubMed  Google Scholar 

  14. Koopman M, Kortman GA, Mekenkamp L, Ligtenberg MJ, Hoogerbrugge N, Mol L et al (2007) Use of microsatellite instability in non-hereditary advanced colorectal cancer to predict response to chemotherapy and overall survival: A study of the Dutch Colorectal Cancer Group (DCCG). J Clin Oncol (Meeting Abstracts) 25:4118

    Google Scholar 

  15. Jensen LH, Danenberg KD, Danenberg PV, Jakobsen A (2007) Predictive value of MSH2 gene expression in colorectal cancer treated with capecitabine. Clin Colorectal Cancer 6:433–435

    Article  CAS  PubMed  Google Scholar 

  16. Compton C, Pettigrew N, Fielding LP (2000) American Joint Committee on Cancer prognostic factors consensus conference. Cancer 88:1739–1757

    Article  CAS  PubMed  Google Scholar 

  17. Halling KC, French AJ, McDonnell SK, Burgart LJ, Schaid DJ, Peterson BJ et al (1999) Microsatellite Instability and 8p allelic imbalance in stage B2 and C colorectal cancers. J Natl Cancer Inst 91:1295–1303

    Article  CAS  PubMed  Google Scholar 

  18. Lynch HT, Smyrk TC, Watson P, Lanspa SJ, Lynch JF, Lynch PM et al (1993) Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: An updated review. Gastroenterology 104:1535–1549

    CAS  PubMed  Google Scholar 

  19. Muller CI, Schulmann K, Reinacher-Schick A, Andre N, Arnold D, Tannapfel A et al (2008) 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 23(11):1033–1039

    Article  CAS  PubMed  Google Scholar 

  20. Baddi L, Benson A III (2005) Adjuvant therapy in stage II colon cancer: Current approaches. Oncologist 10:325–331

    Article  PubMed  Google Scholar 

  21. 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 349:247–257

    Article  CAS  PubMed  Google Scholar 

  22. Sargent DJ, Marsoni S, Thibodeau SN, Labianca R, Hamilton SR, Torri V et al (2008) Confirmation of deficient mismatch repair (dMMR) as a predictive marker for lack of benefit from 5-FU based chemotherapy in stage II and III colon cancer (CC): A pooled molecular reanalysis of randomized chemotherapy trials. J Clin Oncol (Meeting Abstracts) 26:4008

    Google Scholar 

  23. Des Guetz G, Uzzan B, Nicolas P, Schischmanoff P, Morere JF (2008) Microsatellite instability as a predictor of chemotherapy efficacy in colorectal cancer. J Clin Oncol (Meeting Abstracts) 26:4117

    Google Scholar 

Download references

Conflict of interest statement

No funds were received in support of this study.

Author information

Authors and Affiliations

  1. Departments of Oncology, APHP, Hôpital Avicenne, 125 route de Stalingrad, 93009,, Bobigny, France

    Gaëtan Des Guetz & Jean-François Morere

  2. Department of Pharmacology, APHP, Hôpital Avicenne, 125 route de Stalingrad, 93009, Bobigny, France

    Bernard Uzzan & Patrick Nicolas

  3. Department of Biochemistry, APHP, Hôpital Avicenne, 125 route de Stalingrad, 93009, Bobigny, France

    Olivier Schischmanoff

Authors
  1. Gaëtan Des Guetz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bernard Uzzan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patrick Nicolas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Olivier Schischmanoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jean-François Morere
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gaëtan Des Guetz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Des Guetz, G., Uzzan, B., Nicolas, P. et al. Microsatellite instability: a predictive marker in metastatic colorectal cancer?. Targ Oncol 4, 57–62 (2009). https://doi.org/10.1007/s11523-008-0103-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11523-008-0103-8

Keywords

Search

Navigation