Relationship between microsatellite instability, response and survival in palliative patients with colorectal cancer undergoing first-line chemotherapy

Anticancer Res. 2003 Mar-Apr;23(2C):1773-7.

Abstract

Background and aims: The aim of this work was to investigate the relationship between microsatellite instability (MSI), treatment response and survival in palliative patients with colorectal cancer (CRC) undergoing first-line treatment with weekly 24-hour infusion (24-h inf.) of high-dose 5-fluorouracil (5-FU) and folinic acid (FA).

Patients and methods: Tumour material from the colorectal primary carcinomas was analysed for 43 patients. MSI analysis was carried out and immunohistochemistry was performed with hMLH1 and hMSH2.

Results: Tumours of 7 patients (16%) were highly instable (MSI-H). These patients had a better response rate (72% vs. 41%; p = 0.072) and a significantly better median survival (33 months, [95% CI 20-46] vs. 19 months, [95% CI 10-28]; p = 0.021) than microsatellite stable (MSS) patients (n = 36). Furthermore, MSI status was shown to be an independent predictive marker for survival (p = 0.037).

Conclusion: These data provide further support for the hypothesis that MSI-H CRC might have a better response and survival than (MSS) CRC in palliative first-line treatment.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carrier Proteins
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • DNA-Binding Proteins*
  • Drug Administration Schedule
  • Female
  • Fluorouracil / administration & dosage
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Infusions, Intravenous
  • Leucovorin / administration & dosage
  • Male
  • Microsatellite Repeats / genetics*
  • Middle Aged
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Neoplasm Proteins / biosynthesis
  • Nuclear Proteins
  • Palliative Care*
  • Proportional Hazards Models
  • Proto-Oncogene Proteins / biosynthesis
  • Survival Rate
  • Treatment Outcome

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA-Binding Proteins
  • MLH1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Leucovorin
  • Fluorouracil