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

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.

• Authors: W M Brueckl, C Moesch, T Brabletz, C Koebnick, C Riedel, A Jung, S Merkel, S Schaber, F Boxberger, T Kirchner, W Hohenberger, E G Hahn, A Wein
• Journal: Anticancer research (Anticancer Res) 2003 Mar-Apr Vol. 23 Issue 2C Pg. 1773-7 ISSN: 0250-7005 [Print] Greece
• PMID: 12820457 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• Adaptor Proteins, Signal Transducing
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carrier Proteins
• Colorectal Neoplasms (drug therapy, genetics, 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