Staining Patterns of Anti-Apoptotic Protein Beclin-1 in Inflammatory Bowel Disease Associated Dysplasia and Carcinoma
Phoebe J Holmes, Ankit V Gandhi, Juan P Palazzo. Thomas Jefferson University Hospital, Philadelphia, PA
Background: Beclin-1 plays a role in vesicle assembly during autophagy, a type of programmed cell death. It has been shown to be downnregulated in several types of cancer (breast, prostate, and ovarian) and upregulated in gastric and colorectal cancers. This reflects the complex role of autophagy, and more specifically, Beclin 1, in the development and progression of cancer. Autophagy can inhibit apoptosis but also can result in an alternative cell death pathway and protect against carcinogenesis. The diagnosis and progression of inflammatory bowel disease (IBD) to dysplasia and cancer is important in order to identify and treat patents as early as possible. In this study we investigated the expression of Beclin-1 in patients with IBD with dysplasia and cancer in order to elucidate its possible role in this progression.
Design: We studied 64 patients with inflammatory bowel disease who underwent either a biopsy or surgical resection from 1976-1999 at TJUH. 7 patients had inactive disease, 16 had chronic active colitis, 28 had low grade dysplasia, 3 had high grade dysplasia, and 10 had invasive carcinoma. All sections were stained for Beclin-1 (1:200, EPR1733Y, Epitomics, Burlingame, CA) with appropriate controls. Cytoplasmic staining was considered positive. We determined the intensity of staining (0 to 3+) and the distribution of staining (negative, focal, or diffuse). The study was approved by the IRB.
Results: Moderate or strong cytoplasmic staining was seen in 45/57 (79%) cases with chronic active colitis, dysplasia or cancer. Weak, focal, or negative staining was seen in 5/7 (71%) cases of non-inflamed mucosa. The majority of cases of chronic active colitis (81%), 74% of the dysplastic cases, and 90% of the cancers had moderate or strong diffuse staining patterns.
Conclusions: The increased expression of Beclin-1 seen in patients with active colitis, dysplasia, and cancer in patients with IBD supports the notion that autophagic mechanisms play a role in the progression of dysplasia and carcinoma. Increased inflammation and subsequent cell damage present in patients with inflammatory bowel disease may have a role in upregulating Beclin-1 and autophagy and protecting the cells against apoptotic stimuli that would normally induce cell death. Increased Beclin staining may be a marker for progression of inflamed mucosa to dysplasia and carcinoma in IBD patients.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 139, Tuesday Afternoon