In vivo effects of mesalazine or E. coli Nissle 1917 on microsatellite instability in ulcerative colitis

Aliment Pharmacol Ther. 2009 Sep 15;30(6):634-42. doi: 10.1111/j.1365-2036.2009.04076.x. Epub 2009 Jun 25.

Abstract

Background: Microsatellite instability (MSI) occurs in chronically inflamed colorectal tissue and may evolve to colitis-associated cancer. In vitro data suggest that mesalazine (5-ASA) improves MSI.

Aim: To analyse the changes in MSI in 156 distal colonic biopsies of 39 patients with ulcerative colitis that had been treated within a randomized, double-blind trial comparing 5-ASA with E. coli Nissle (EcN).

Methods: Two biopsies had been collected before and after 1 year of treatment. MSI testing was performed using a panel of eight markers, including 3 dinucleotide and 5 mononucleotide repeats.

Results: No MSI was observed with any of the mono-repeats, and among dinucleotide repeats, only D5S346 (maps to APC) and D17S250 (p53) were consistently informative. Overall, 31/156 (20%) biopsies displayed MSI. After 1 year, 3/11 patients displayed MSI improvement [change to microsatellite stability (MSS); 1 on 5-ASA, 2 on EcN] at D5S346 and 4/11 showed MSI worsening (change from MSS to MSI; all 5-ASA). For D17S250, the corresponding data were for 3/9 patients (2 on 5-ASA, 1 on EcN) and 2/9 (both on 5-ASA), respectively.

Conclusions: In the set of biopsies taken from patients treated with 1.5 g 5-ASA for 1 year, there was no improvement in the prevalence of MSI in the distal colon.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Biopsy
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / pathology
  • Colon / pathology
  • Double-Blind Method
  • Estranes / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Loss of Heterozygosity
  • Male
  • Mesalamine / therapeutic use*
  • Microsatellite Instability / drug effects*
  • Microsatellite Repeats / drug effects*
  • Middle Aged
  • Nitriles / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • 17-hydroxyestrane-3-carbonitrile
  • Anti-Inflammatory Agents, Non-Steroidal
  • Estranes
  • Nitriles
  • Mesalamine