Differentiation pathways in duodenal and ampullary carcinomas: a comparative study on mucin and trefoil peptide expression, including gastric and colon carcinomas

Gürbüz, Yeşim; Klöppel, Günter

doi:10.1007/s00428-004-1008-2

Cited by 20 publications

(4 citation statements)

References 29 publications

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“…In the present study, almost all of ELF3 mutations were truncating, suggesting that inactivation of this gene could drive ampullary tumorigenesis. The ampulla of Vater sits at the intersection of pancreatobiliary and intestinal differentiation (Gürbüz and Klöppel, 2004), and it is therefore of interest to note that, in the ELF3 -null mice model, inactivation of ELF3 results in dysmorphogenesis and altered differentiation of small intestinal epithelium (Ng et al, 2002). Elf3 is critical for proper epithelial differentiation in pancreas as well as intestine (Kobberup et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma

et al. 2016

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SUMMARY Ampullary carcinomas are highly malignant neoplasms that can have either intestinal or pancreatobiliary differentiation. To characterize somatic alterations in ampullary carcinomas, we performed whole-exome sequencing and DNA copy number analysis on 60 ampullary carcinomas resected from clinically well-characterized Japanese and American patients. We next selected 92 genes and performed targeted-sequencing to validate significantly mutated genes in additional 112 cancers. The prevalence of driver gene mutations in carcinomas with the intestinal phenotype is different from those with the pancreatobiliary phenotype. We identified a characteristic significantly mutated driver gene (ELF3) as well as previously known driver genes (TP53, KRAS, APC and others). Functional studies demonstrated that ELF3 silencing in normal human epithelial cells enhances their motility and invasion.

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Section: Discussionmentioning

confidence: 99%

Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma

et al. 2016

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“…The histological differentiation is a key factor in the prognosis of ampullary cancer [2]. The intestinal subtype is negative for MUC1 and the biliopancreatic subtype is negative for MUC2 [2,5-7]. The differing expression of mucins in ampullary adenocarcinomas is attributed to the development of histogenetically differing carcinomas that come from the intestinal or the pancreaticobiliary mucosa.…”

Section: Introductionmentioning

confidence: 99%

Mucins Differently Expressed in Various Ampullary Adenocarcinomas

Wang

Liang

et al. 2011

Diagn Pathol

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BackgroundWe investigated the occurrence and clinical significance of mucin expression in ampullary adenocarcinoma.MethodsWe retrospectively analyzed clinical, pathological, and survival data from 74 ampullary adenocarcinoma patients who received radical operation from January 2004 to November 2006.ResultsThe tumors were located in the lower end of the common bile duct (46%), papillary duodenum (42%), and ampullary duodenum (12%), and expressed MUC1 (72%), MUC2 (20%), MUC5AC (43%), and MUC6 (27%). Expression of MUC1 was associated with tumor differentiation (OR: 4.71, 95% CI: 1.26, 17.66, P = 0.021). Expression of MUC5AC was associated with age (OR: 1.07, 95% CI: 1.11, 1.14, P = 0.026) and less vessel invasion(OR: 0.14, 95% CI: 0.03, 0.72, P = 0.019). The survival rates were not significantly different when patients had or had no expression of MUC1, MUC2, MUC5AC, or MUC6 in tumor. Patients with tumors positive for MUC5AC in the papillary duodenum had worse survival than those with tumors negative for MUC5AC (P = 0.044).ConclusionsExpression of MUC1 was high (72%) in ampullary adenocarcinoma, while expressions of MUC2, MUC5AC, and MUC6 were lower. Mucins are useful markers to diagnose and identify ampullary adenocarcinoma, particularly in determining the degree of malignancy of ampullary adenocarcinoma.

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“…Recently, the aberrant expression of mucin ( MUC ) gene products in adenomas and carcinomas of the colorectum has been investigated as a potential source of tissue biomarkers to improve serrated polyp subclassification 5,6. Mucins are high molecular weight epithelial glycoproteins that are classified into two distinct structural and functional classes: secreted gel-forming mucins and transmembrane mucins.…”

Section: Introductionmentioning

confidence: 99%

Expression of gastric pyloric mucin, MUC6, in colorectal serrated polyps

et al. 2010

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Serrated polyps of the colorectal mucosa represent a heterogeneous and controversial taxonomic category with variation in histopathologic, molecular, and immunohistochemical characteristics and with incomplete understanding of pathogenesis. A previous study reported that expression of gastric pyloric-type mucin MUC6 characterized sessile serrated adenomas. We therefore evaluated the expression of MUC6 in serrated polyps identified among 2,502 participants in a Phase III chemoprevention trial within the Arizona Cancer Center Colorectal Cancer Prevention Trials Program and characterized the associated histopathologic features and location. We performed immunohistochemistry for MUC6 on 146 serrated lesions and 87 conventional tubular adenomas and assessed the percentage of cells with expression and the grade of staining intensity. Ninety-two hyperplastic polyps, 43 sessile serrated adenomas, and 11 traditional serrated adenomas were included. Polyps ranged in size from 1 to 150 millimeters. The association of MUC6 staining with serrated polyp category was evaluated using classification and regression tree (CART) analysis and two-sided Fisher’s exact test. 53% of sessile serrated adenomas (n=23), 17 % of hyperplastic polyps (n=16), and 18% of traditional serrated adenomas (n=2) but none of 87 tubular adenomas expressed MUC6. Expression was limited to the lower crypts in all serrated polyps. Extent of positive staining ranged from 2–100% of crypt cells and was independent of histopathologic type. MUC6 expression had relatively high specificity for sessile serrated adenoma (82%) but low sensitivity (54%). In CART analysis, proximal location was found to be the best partitioning factor for MUC6, followed by classification as sessile serrated adenoma. We conclude that MUC6 expression is strongly associated with proximal location of serrated polyps but has only modest utility as a tissue biomarker for sessile serrated adenoma.

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Differentiation pathways in duodenal and ampullary carcinomas: a comparative study on mucin and trefoil peptide expression, including gastric and colon carcinomas

Cited by 20 publications

References 29 publications

Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma

Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma

Mucins Differently Expressed in Various Ampullary Adenocarcinomas

Expression of gastric pyloric mucin, MUC6, in colorectal serrated polyps

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