Loss or Decreased Expression of Aldo-Keto Reductase Family 1 B10 Protein in Ulcerative Colitis: A Potential Susceptibility Gene to Ulcerative Colitis
SD Norwood, J Liao, HN Li, MS Rao, G-Y Yang. Northwestern University Feinberg School of Medicine, Chicago, IL
Background: Aldo-keto reductase family 1 B10 (AKR1B10) protein acts as an enzyme that detoxifies reactive free radical carbonyl compounds. Expression of AKR1B10 protein in intestinal surface epithelium protects against cytotoxic carbonyl compounds derived from intracellular lipid peroxidation, the diet and gut microbes. Free radicals, such as carbonyls, play a key pathogenic process in ulcerative colitis (UC), however the role of AKR1B10 in UC is not known. Here, we studied the expression of AKR1B10 in colonic epithelium of active chronic UC compared to normal colonic epithelium, and showed that decreased expression of this protective enzyme may contribute to cellular damage.
Design: A one-to-one case-control cohort, matched for age and gender, was designed to compare active chronic UC versus normal colon. 50 colon specimens (from biopsies & resections) with the diagnosis of "active chronic ulcerative colitis" (19 male and 31 female) were collected; and 50 colon specimens, matched for age and gender, with histologically normal colonic epithelium were also collected. Immunohistochemistry was performed on the 100 specimens with AKR1B10 antibody. The staining of the colonic surface epithelium was classified as no staining/loss of expression (0), low intensity staining/decreased expression (L) or high intensity staining/high expression (H).
Results: AKR1B10 was expressed as cytoplasmic staining in the epithelial cells of the top 1/3 of colonic epithelium but not in colonic crypts. The results showed that 20% (n=10) of UC specimens displayed loss of expression of AKR1B10, and 64% (n=32) and 16% (n=8) exhibited low and high intensity staining. In the normal colon, 2% (n=1) of specimens showed loss expression of AKR1B10, and 38% (n=19) and 60% (n=30) showed low and high intensity staining. The differences between no staining and low/high staining (0 vs L/H) as well as low staining and high staining (L vs H) in UC vs normal colon was statistically significant, (p<0.0078) and (p< 0.0001), using Fisher's exact test.
Conclusions: The decreased expression of AKR1B10 in UC, as shown by no staining and low staining, compared to normal colon is suggestive of a genetic alteration either leading to no expression or decreased expression of AKR1B10. This finding suggests that AKR1B10 is a possible susceptibility gene for UC, and that loss of expression could lead to loss of protection from damaging free radicals. Further, AKR1B10 could also be a useful biomarker for UC.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 101, Monday Morning