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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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.
KeywordsColorectal cancer Microsatellite instability Chemotherapy Prognosis
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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