GI04 - Evaluation of KI-67, Goblet Cell and MUC2 Mucin Expression in Canine Lymphoplasmacytic and Granulomatous Colitis

Abstract: Background: It is unknown if Ki-67 expression shows potential as a marker of intestinal inflammation, or if goblet cell (GbC) depletion correlates with decreased MUC2 mucin expression or inflammation severity in dogs with chronic colitis.

Objectives: To compare Ki-67, GbC and MUC2 expression in endoscopic biopsies from dogs with granulomatous colitis (GC), lymphoplasmacytic colitis (LPC), and normal colon (NC).

Animals: 48 client-owned dogs [GC (n= 19), LPC (n=19), NC (n=10)].

Methods: Sections of formalin-fixed, paraffin-embedded endoscopic colonic biopsies were stained using Ki-67 immunohistochemistry; RNAscope in-situ hybridization was performed using customized canine MUC2-targeted probes. Five microscopic fields per dog were selected for measuring Ki-67 labelling index (Ki67%), proportions of GbC staining (Gbc%) and MUC2-positive cell staining (MUC2%) using image analysis software (FIJI). Data was analyzed using Pearson’s correlation and linear regression.

Results: Median normalised Ki67% in NC dogs (6.69%; 95%-CI, 2.94-12.72%), was higher compared to LPC (4.91%; 95%-CI, 3.94-7.89%) and GC dogs (1.13%; 95%-CI, 0.79-2.04%). Median GbC% did not correlate with severity of colonic inflammation overall. MUC2 expression was highest in NC dogs. Colonic inflammation was associated with markedly decreased MUC2 expression in LPC (r=-0.917; 95%-CI, -0.991–-0.411) but not GC dogs (r=0.078; 95%-CI, -0.663–0.742). MUC2% and GbC% were positively correlated in NC (r=0.911; 95%-CI, 0.503–0.987) but not GC and LPC dogs.

Conclusion: Variations in MUC2 expression between GC and LPC dogs reflect differences in pathways regulating MUC2 biosynthesis and secretion. MUC2 expression levels with GC and LPC are influenced by mechanisms modulating GbC function rather than quantity.