Instability of Non-Standard Microsatellites in Relation to Prognosis in Metastatic Colorectal Cancer Patients

Int J Mol Sci. 2020 May 16;21(10):3532. doi: 10.3390/ijms21103532.

Abstract

Very few data are reported in the literature on the association between elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) and prognosis in advanced colorectal cancer. Moreover, there is no information available in relation to the response to antiangiogenic treatment. We analyzed EMAST and vascular endothelial growth factor-B (VEGF-B) microsatellite status, together with standard microsatellite instability (MSI), in relation to prognosis in 141 patients with metastatic colorectal cancer (mCRC) treated with chemotherapy (CT) alone (n = 51) or chemotherapy with bevacizumab (B) (CT + B; n = 90). High MSI (MSI-H) was detected in 3% of patients and was associated with progression-free survival (PFS; p = 0.005) and overall survival (OS; p < 0.0001). A total of 8% of cases showed EMAST instability, which was associated with worse PFS (p = 0.0006) and OS (p < 0.0001) in patients treated with CT + B. A total of 24.2% of patients showed VEGF-B instability associated with poorer outcome in (p = 0.005) in the CT arm. In conclusion, our analysis indicated that EMAST instability is associated with worse prognosis, particularly evident in patients receiving CT + B.

Keywords: EMAST; MSI; VEGF-B; combinatorial therapy; mCRC.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bevacizumab / therapeutic use
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / secondary*
  • Female
  • Humans
  • Male
  • Microsatellite Instability*
  • Microsatellite Repeats / genetics
  • Middle Aged
  • Prognosis
  • Progression-Free Survival
  • Treatment Outcome
  • Vascular Endothelial Growth Factor B / genetics

Substances

  • VEGFB protein, human
  • Vascular Endothelial Growth Factor B
  • Bevacizumab