| Since most cases of colitis-associated cancer (CAC) arise from dysplasia, surveillance colonoscopy is recommended to detect dysplasia. Recently, it was suggested that intensified surveillance and endoscopic resection of dysplasia might prevent CAC. If we can reliably predict an individual's risk of CAC and endoscopically resect dysplasia, surveillance strategies could improve quality of life. The aims are to predict cancer risk and to determine indications for endoscopic resection of dysplasia. We analyzed gene expression of colon tissues obtained from 324 patients with ulcerative colitis (UC) and CAC and found that expression of stress response proteins (HSPA4, Cirp, RBM3), stem cell marker Bmi1 and oncoprotein gankyrin was enhanced in colonic mucosa of patients with refractory UC that is closely related to high risk for cancer. Consistently, these molecules were upregulated in CAC tissues and promoted tumorigenesis in murine CAC models, suggesting a potential biomarker for predicting the risk of CAC development. Then, we had 8 cases of colitis-associated dysplasia/cancer (5 intra-mucosal carcinoma/dysplasia and 3 invasive cancer) during surveillance colonoscopy. Analysis using Ion AmpliSeq Cancer Hotspot Panel v2 identified TP53 or PIK3CA mutations in all cases. Out of the 5 intra-mucosal carcinoma/dysplasia, 4 lesions whose margins were visible and conspicuous were endoscopically resected without any complications or local recurrence. Taken together, risk stratification and appropriate endoscopic treatment of dysplasia would make a new strategy to personalize surveillance program for CAC. |
