Abstract
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.
Highlights
Most small intestine adenomas, including the ampulla of Vater, develop in the duodenum
We clarified the expression of β-catenin and aldehyde dehydrogenase 1 (ALDH1) in sporadic adenomas and adenocarcinomas in non-ampullary duodenal lesions by IHC
We have suggested the pathogenesis in sporadic non-ampullary duodenal adenoma and adenocarcinoma(Figure 6)
Summary
Most small intestine adenomas, including the ampulla of Vater, develop in the duodenum. Sporadic non-ampullary (except the ampulla of Vater) duodenal adenomas are uncommon [1, 2] compared to adenomas in familial adenomatous polyposis (FAP), with a germline mutation in the adenomatous polyposis coli www.impactjournals.com/oncotarget (APC) gene. 60% of duodenal adenomas develop in patients with FAP, while the remaining 40% are sporadic [3]. Non-ampullary duodenal adenoma is thought to be a precancerous lesion, and the model of the adenoma-carcinoma sequence is predicted to involve the small intestine, including the duodenum and colorectum [4,5,6]. By APC and CTNNB1 gene mutation, is associated with early events in colon carcinogenesis in the model of the adenomacarcinoma sequence [9]. Nuclear β-catenin translocation increased with the progression of colorectal tissue from normal epithelial tissue, adenomas, to carcinomas in the colorectum [10]
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