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In vivo effects of mesalazine or E. coli Nissle 1917 on microsatellite instability in ulcerative colitis
A Goel1, A Mittal, R Evstatiev
1Division of Gastroenterology, Department of Internal Medicine and Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, TX 75246, USA.
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.
Insights
Mesalazine (5-ASA) did not improve microsatellite instability (MSI) in ulcerative colitis patients after one year. While some patients showed MSI improvement or worsening, the overall prevalence of MSI in the distal colon remained unchanged.
Area of Science:
- Gastroenterology
- Oncology
- Molecular Biology
Background:
- Microsatellite instability (MSI) is linked to chronic inflammation in colorectal tissue and may progress to colitis-associated cancer.
- In vitro studies suggest mesalazine (5-ASA) can improve MSI.
- Ulcerative colitis (UC) patients are at increased risk for colorectal cancer.
Purpose of the Study:
- To analyze changes in MSI in distal colonic biopsies from UC patients treated with 5-ASA or E. coli Nissle (EcN).
- To evaluate the efficacy of 5-ASA in improving MSI in the context of ulcerative colitis.
Main Methods:
- 156 distal colonic biopsies from 39 UC patients were collected before and after 1 year of treatment.
- MSI testing was performed using a panel of eight markers (3 dinucleotide, 5 mononucleotide repeats).
- Two dinucleotide markers (D5S346 and D17S250) were found to be informative for MSI analysis.
Main Results:
- Overall, 20% (31/156) of biopsies displayed MSI.
- After 1 year, 3/11 patients showed MSI improvement to microsatellite stability (MSS) (1 on 5-ASA, 2 on EcN) at D5S346.
- 4/11 patients showed MSI worsening (MSS to MSI) at D5S346 (all on 5-ASA), and similar trends were observed for D17S250.
Conclusions:
- Treatment with 1.5 g of 5-ASA for 1 year did not lead to an improvement in the prevalence of MSI in the distal colon of UC patients.
- The study did not demonstrate a significant benefit of 5-ASA in reducing MSI in this patient cohort.
- Further research may be needed to explore alternative or combination therapies for managing MSI in ulcerative colitis.
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