Low level of microsatellite instability correlates with short disease-free survival of gastric cancer patients undergoing neoadjuvant chemotherapy

Virchows Arch. 2021 Feb;478(2):231-240. doi: 10.1007/s00428-020-02878-6. Epub 2020 Jun 25.

Abstract

Limited studies have been reported about the function of low level of microsatellite instability (MSI-L) in cancer. The aim of our study is to unveil the prognostic role of MSI-L in gastric cancer (GC). One hundred nine patients with locally advanced GC (T3-4a, N+, M0) who underwent neoadjuvant chemotherapy plus gastrectomy with extended (D2) lymph node dissection were collected. Clinicopathological characteristics, tumour regression score, disease-free survival (DFS), and overall survival (OS) were analysed and correlated with the MSI status. The MSI status of 96 patients was identified (7 (7.3%) with MSI-H, 12 (12.5%) with MSI-L, and 77 (80.2%) with MSS). MSI-L was significantly correlated with perineural invasion (P = 0.009) and decreased MUC5AC expression (P = 0.042). Poor response to neoadjuvant chemotherapy in MSI-L patients (83.3% assessed as poor response) was observed (P = 0.501). Compared with patients with MSS tumours, patients with MSI-L tumours showed poor DFS (P = 0.018) with a hazard ratio (HR) of 2.839 (95% CI 1.131-7.124, P = 0.026) from multivariable cox regression analysis. However, this was not associated with OS (P = 0.063). MSI-L is an independent poor prognostic biomarker for the locally advanced gastric cancer treated with neoadjuvant chemotherapy. Further studies with larger sample sizes are needed for validation.

Keywords: Biomarker; Gastric cancer; MSI; Neoadjuvant chemotherapy; Prognosis.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Capecitabine / adverse effects
  • Capecitabine / therapeutic use*
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Female
  • Gastrectomy* / adverse effects
  • Gastrectomy* / mortality
  • Humans
  • Lymph Node Excision* / adverse effects
  • Lymph Node Excision* / mortality
  • Male
  • Microsatellite Instability*
  • Middle Aged
  • Neoadjuvant Therapy* / adverse effects
  • Neoadjuvant Therapy* / mortality
  • Neoplasm Staging
  • Oxaloacetates / adverse effects
  • Oxaloacetates / therapeutic use*
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy*
  • Time Factors

Substances

  • Biomarkers, Tumor
  • Oxaloacetates
  • Capecitabine

Supplementary concepts

  • XELOX