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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

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Abstract

Background and aims

Microsatellite instability (MSI) is a potential indicator of prognosis in patients with colorectal cancer (CRC). To date, there are a limited number of studies which investigated its role in advanced CRC. Our study investigated the value of high degree of MSI (MSI-H) in patients treated with 5-FU/oxaliplatin-based chemotherapy which has been done by only one further study recently.

Patients and methods

In this study, we investigated tumour tissues from 108 patients with metastatic CRC who were treated in a prospective, randomised trial comparing two oxaliplatin and 5-FU-based therapy regimens (FUFOX vs. CAPOX) involving a total of 474 patients. We determined the incidence and prognostic value of a high degree of microsatellite instability. The specimens were analysed by PCR corresponding to the National Institute of Health reference panel. In addition, immunostaining of the mismatch repair proteins MLH1, MSH2 and MSH6 was performed.

Results and findings

The incidence of MSI-H was 4%. MSI-H was correlated with a lower rate of disease control compared to non-MSI-H patients (p = 0.02). However, there was no correlation between MSI-H and progression-free survival or overall survival.

Interpretation and conclusion

MSI-H incidence in metastatic CRC was low. Our data suggest that MSI-H may be correlated with a poorer response to a 5-FU/oxaliplatin treatment. This finding needs confirmation in a larger cohort.

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Acknowledgements and grant support

This study was supported in part by a grant of the German Cancer Aid (Deutsche Krebshilfe, 70–3033-Schm 4) to WS and an intramural research grant of the Medical Faculty of the Ruhr-University Bochum to KS. We thank Sabine Geiger, Hedi Safa, Sandra Grasediek and Britta Redeker for technical assistance and the AIO for providing clinical data. We thank the participating pathologists for providing tissue blocks. The authors state to have no financial disclosures.

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Authors and Affiliations

  1. Institute of Physiology, University Hospital Essen, Essen, Germany

    C. I. Müller

  2. Medical Department, Ruhr-University of Bochum, Knappschaftskrankenhaus, Bochum, Germany

    K. Schulmann, A. Reinacher-Schick, N. Andre & W. Schmiegel

  3. Medical Department IV, University Clinic, Martin Luther University, Halle, Germany

    D. Arnold & S. H.-J. Schmoll

  4. Institute of Pathology, University Clinic Bergmannsheil, Ruhr-University of Bochum, Bochum, Germany

    A. Tannapfel

  5. Drug Development Unit, Royal Marsden Hospital and Institute of Cancer Research, Sutton, UK

    H. Arkenau

  6. Center for Clinical Research (ZKF, Molecular GI-Oncology (MGO)), Ruhr-University of Bochum, Bochum, Germany

    S. A. Hahn

  7. Medical Department Klinikum Bremen-Ost, Bremen, Germany

    R. Porschen

  8. Division of Gastroenterology and Hepatology, University Hospital Bergmannsheil, Ruhr-University of Bochum, Bochum, Germany

    W. Schmiegel

  9. Kliniken Maria Hilf GmbH Klinik für Hämatologie, Onkologie, Gastroenterologie, Krankenhaus St. Franziskus, Viersener Straße 450, 41063, Mönchengladbach, Germany

    U. Graeven

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  1. C. I. Müller
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Corresponding author

Correspondence to U. Graeven.

Additional information

C. I. Müller and K. Schulmann contributed equally to this manuscript.

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Müller, C.I., 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 23, 1033–1039 (2008). https://doi.org/10.1007/s00384-008-0504-2

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