Metastatic Pattern of Stage IV Colorectal Cancer with High-Frequency Microsatellite Instability as a Prognostic Factor

Anticancer Res. 2017 Jan;37(1):239-247. doi: 10.21873/anticanres.11313.


Background: A recent clinical trial on the immune check-point inhibitor pembrolizumab demonstrated that microsatellite instability (MSI) is a good biomarker for response to this inhibitor. However, clinicopathological features of advanced colorectal cancer (CRC) with high-frequency MSI (MSI-H) are unclear.

Patients and methods: A total of 2,439 surgically resected CRC tissues were analyzed for MSI status, and mutational status of V-Ki-Ras2 Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B (BRAF). Stage IV cases were selected, and clinical and molecular features were evaluated.

Results: There was no significant survival difference observed between MSI-H CRC and microsatellite-stable (MSS) CRC in patients with stage IV disease (3.92 vs. 2.50 years; p=0.766). However, hematogenous and lymphogenous metastasis-dominant CRC with MSI-H demonstrated poor prognosis, whereas peritoneal metastasis-dominant CRC with MSI-H demonstrated good prognosis, (1.33 vs. 5.2 years; p=0.006).

Conclusion: Prognosis of stage IV CRC with MSI-H depended on the metastatic pattern. These findings provide useful information for the adaptation of CRC immunotherapy.

Keywords: BRAF mutation; Colorectal cancer; Lynch syndrome; immune-checkpoint inhibitor; microsatellite instability.

MeSH terms

  • Adult
  • Aged
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Female
  • GTP Phosphohydrolases / genetics
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / secondary
  • Lung Neoplasms / genetics
  • Lung Neoplasms / secondary
  • Lymphatic Metastasis
  • Male
  • Membrane Proteins / genetics
  • Microsatellite Instability*
  • Middle Aged
  • MutL Protein Homolog 1 / genetics
  • Mutation
  • Neoplasm Staging
  • Peritoneal Neoplasms / genetics
  • Peritoneal Neoplasms / secondary
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics


  • KRAS protein, human
  • MLH1 protein, human
  • Membrane Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • GTP Phosphohydrolases
  • NRAS protein, human
  • MutL Protein Homolog 1
  • Proto-Oncogene Proteins p21(ras)