Intestinal S100/Calgranulin Expression in Cats with Chronic Inflammatory Enteropathy and Intestinal Lymphoma

SIMPLE SUMMARY: Intestinal diseases in cats are complicated diseases in which intestinal inflammation is difficult to distinguish from lymphoma, which is a neoplasm. In this study, the expression of the proteins S100A8/A9 and S100A12 (also called calgranulins) in the intestine is investigated in both diseases and for potential correlations with microscopically visible changes in the intestine or the clinical severity of the disease. Only small differences were seen between healthy and diseased animals, and there were no differences between cats with intestinal inflammation and lymphoma. However, several correlations of cells staining positive for calgranulins and inflammatory changes at the microscopic level and clinical disease severity were shown. This indicates that calgranulins play a role in both gastrointestinal lymphoma and inflammation and would support the recent theory that these two diseases might not be separate disease entities but instead are related. Further insights into the role of the calgranulins in these feline diseases will lead to a better understanding of the disease pathogenesis and, thus, potentially novel diagnostics and treatment avenues. ABSTRACT: Diagnosing chronic inflammatory enteropathies (CIE) in cats and differentiation from intestinal lymphoma (IL) using currently available diagnostics is challenging. Intestinally expressed S100/calgranulins, measured in fecal samples, appear to be useful non-invasive biomarkers for canine CIE but have not been evaluated in cats. We hypothesized S100/calgranulins to play a role in the pathogenesis of feline chronic enteropathies (FCE) and to correlate with clinical and/or histologic disease severity. This retrospective case-control study included patient data and gastrointestinal (GI) tissues from 16 cats with CIE, 8 cats with IL, and 16 controls with no clinical signs of GI disease. GI tissue biopsies were immunohistochemically stained using polyclonal α-S100A8/A9 and α-S100A12 antibodies. S100A8/A9(+) and S100A12(+) cells were detected in all GI segments, with few significant differences between CIE, IL, and controls and no difference between diseased groups. Segmental inflammatory lesions were moderately to strongly correlated with increased S100/calgranulin-positive cell counts. Clinical disease severity correlated with S100A12(+) cell counts in cats with IL (ρ = 0.69, p = 0.042) and more severe diarrhea with colonic lamina propria S100A12(+) cells with CIE (ρ = 0.78, p = 0.021) and duodenal S100A8/A9(+) cells with IL (ρ = 0.71, p = 0.032). These findings suggest a role of the S100/calgranulins in the pathogenesis of the spectrum of FCE, including CIE and IL.