1. Expression of ATF6 as a marker of pre-cancerous atypical change in ulcerative colitis-associated colorectal cancer: a potential role in the management of dysplasia
- Author
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Hiroyuki Uetake, Masamichi Yasuno, Akifumi Kikuchi, Michiyo Tokura, Megumi Ishiguro, Tatsuyuki Kawano, Toshiaki Ishikawa, Shinichi Yamauchi, and Marie Hanaoka
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Original Article—Alimentary Tract ,Adenoma ,Male ,0301 basic medicine ,Dysplasia ,Pathology ,medicine.medical_specialty ,Colon ,Colorectal cancer ,education ,Inflammatory bowel disease ,Unfolded protein response ,03 medical and health sciences ,0302 clinical medicine ,Intestinal mucosa ,medicine ,Atypia ,Humans ,Intestinal Mucosa ,Colitis ,ATF6 ,Aged ,Management of ulcerative colitis ,business.industry ,Gastroenterology ,Middle Aged ,medicine.disease ,Ulcerative colitis ,digestive system diseases ,Activating Transcription Factor 6 ,030104 developmental biology ,030220 oncology & carcinogenesis ,Colitis, Ulcerative ,Female ,Tumor Suppressor Protein p53 ,Colorectal Neoplasms ,business ,Precancerous Conditions ,Biomarkers - Abstract
Background Diagnosis of low-grade dysplasia (LGD) is important in the management of ulcerative colitis (UC), but it is often difficult to distinguish LGD from inflammatory regenerative epithelium. The unfolded protein response (UPR) is activated in inflammatory bowel disease and malignancies. We aimed to identify a UPR-related gene that is involved in the development of non-UC and UC-associated colorectal cancer (CRC), and to investigate whether the target gene is useful for the diagnosis of LGD. Methods Using our microarray gene expression database of 152 CRCs, we identified activating transcription factor 6 (ATF6) as a target gene. Immunohistochemistry (IHC) of ATF6 were analyzed in 137 surgically resected CRCs, 95 endoscopically resected adenomas and pTis cancers, and 136 samples from 51 UC patients (93 colitis without neoplasia, 31 dysplasia, and 12 UC-associated CRC). The diagnostic accuracy of ATF6 and p53 as markers of LGD was assessed. Results ATF6 expression was detectable in all CRCs but not in normal colonic mucosa, was elevated with increase in cellular atypia (adenoma with moderate atypia < severe atypia < pTis CRC, p
- Published
- 2017
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