Abstract
Microsatellite instability (MSI) is a marker of the replication error phenotype. It is caused by impaired DNA mismatch repair processes (MMR), resulting in ineffectiveness of the mechanisms responsible for the DNA replication precision and postreplicative DNA repair. MSI underlies the pathogenesis of 10%–20% of colorectal cancer (CRC) cases. The data about the potential value of MMR status as a predictive factor for 5-fluorouracil (FU)-based chemotherapy remain unclear. According to National Comprehensive Cancer Network updated guidelines, MSI testing is recommended for all patients with stage II CRC because patients with MSI-H (high-frequency MSI) tumour may have a good prognosis and obtain no benefit from 5-FU-based adjuvant chemotherapy. The significance of the MSI status as a predictive factor for patients with metastatic disease was not confirmed. The association between the MSI status and the efficacy of the therapy based on anti-programmed death-1 receptor inhibitors requires further studies.
Highlights
Colorectal cancer (CRC) is a heterogeneous disease with significant differences between clinical presentation, prognosis and individual treatment response, even at the same pathological stage
It seemed that the prognosis could be different in the subtypes of CRC depending on Microsatellite instability (MSI)/mismatch repair processes (MMR), KRAS and BRAF status [29,31,34]
According to the National Comprehensive Cancer Network (NCCN) guidelines, MSI testing is recommended for all patients with stage II CRC, which is based on the assumption that these individuals obtain no benefit from 5-FU-based adjuvant therapy [44] based on the results obtained by Sargent et al [7]
Summary
Colorectal cancer (CRC) is a heterogeneous disease with significant differences between clinical presentation, prognosis and individual treatment response, even at the same pathological stage. The increase in BRAF mutation in metastatic MSI cancer compared to early stage reflects a more aggressive phenotype It seemed that the prognosis could be different in the subtypes of CRC depending on MSI/MMR, KRAS and BRAF status [29,31,34]. The findings of the early clinical trials did not confirm these observations, suggesting a possible better survival in the group of patients with MSI tumours receiving 5-FU compared to the MSS CRC group [52,69,70,71] It is explained by some authors as potential enhancement of better prognosis noted frequently in patients with MSI CRC [1].
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