The different pathogenesis of sporadic adenoma and adenocarcinoma in non-ampullary lesions of the proximal and distal duodenum
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Ayumi Niwa1,*, Seiya Kuwano1,*, Hiroyuki Tomita1, Keita Kimura1, Yukiya Orihara1, Tomohiro Kanayama1, Kei Noguchi1, Kenji Hisamatsu1, Takayuki Nakashima1, Yuichiro Hatano1, Akihiro Hirata2, Tatsuhiko Miyazaki3, Kazuhiro Kaneko4, Takuji Tanaka5 and Akira Hara1
1Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan
2Division of Animal Experiment, Life Science Research Center, Gifu University, Gifu, Japan
3Division of Pathology, Gifu University Hospital, Gifu, Japan
4Department of Gastroenterology, Endoscopy Division, National Cancer Center Hospital East, Kashiwa, Japan
5Department of Diagnostic Pathology (DDP) and Research Center of Diagnostic Pathology (RC-DiP), Gifu Municipal Hospital, Gifu, Japan
*These authors have contributed equally to this work
Hiroyuki Tomita, email: [email protected]
Keywords: duodenal neoplasms, beta-catenin
Received: October 24, 2016 Accepted: February 27, 2017 Published: April 12, 2017
Non-ampullary duodenal adenoma with activation of Wnt/β-catenin signalling is common in familial adenomatous polyposis (FAP) patients, whereas sporadic non-ampullary adenoma is uncommon. The adenoma-carcinoma sequence similar to colon cancer is associated with duodenal tumors in FAP, but not always in sporadic tumors. We obtained 37 non-ampullary duodenal tumors, including 25 adenomas and 12 adenocarcinomas, were obtained from biopsies and endoscopic resections. We performed immunohistochemistry for β-catenin, the hallmark of Wnt activation, and aldehyde dehydrogenase 1 (ALDH1), a putative cancer stem cell marker. In non-ampullary lesions, abnormal nuclear localization of β-catenin was observed in 21 (84.0%) of 25 adenomas and 4 (33.3%) of 12 adenocarcinomas. In the proximal duodenum, nuclear β-catenin was less frequent in both adenomas and adenocarcinomas. Gastric duodenal metaplasia (GDM) was observed only in the proximal duodenum. All adenomas with GDM were the gastric foveolar and pyloric gland types, and showed only membranous β-catenin. The intestinal-type adenomas had nuclear β-catenin in the proximal and distal duodenum. ALDH1-positive cells were more frequent in adenocarcinomas than adenomas. Nuclear β-catenin accumulation frequently occurred in ALDH1-positive cells in adenoma, but not in adenocarcinoma. In the non-ampullary proximal duodenum, Wnt/β-catenin pathway activation was more closely associated with adenomas than adenocarcinomas, and while it might cooperate with ALDH1 in adenoma, it does not in adenocarcinoma. The pathogenesis thus may differ between sporadic adenoma and adenocarcinoma of non-ampullary duodenal lesions, especially in the proximal and distal duodenum.
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