ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2015
Sequencing of 279 cancer genes in ampullary carcinoma reveals trends relating to histologic subtypes and frequent amplification and overexpression of ERBB2 (HER2).
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: a potential therapeutic target?Cancer metastasis reviews · 2017Pooled it
- Comprehensive Clinicopathologic, Immunohistochemical, and Genomic Profiling of Sporadic Ampullary Somatostatin-producing D-cell Neuroendocrine Tumors Identifies Recurrent HRAS Hotspot Mutations.Endocrine pathology · 2026Article
- Tumours of the duodenum and the ampulla of Vater: An overview of the key criteria for their classification, pathogenesis, and molecular assessment.Virchows Archiv : an international journal of pathology · 2026Review
- Tumor-Agnostic Landscape withCurrent oncology (Toronto, Ont.) · 2026Observational
- Rare, Yet Targetable: New Perspectives on Ampullary Carcinomas.International journal of molecular sciences · 2026Review
- Research on Targeted Therapy for Malignant Tumors of the Biliary Tract.OncoTargets and therapy · 2026Review
- Article
- Clinicomolecular Profile and Efficacy of Human Epidermal Growth Factor Receptor 2 (HER2)-Targeted Therapy forJCO precision oncology · 2025Article
- Integrated proteogenomic characterization of ampullary adenocarcinoma.Cell discovery · 2025Article
- The Immune Landscape and Its Potential for Immunotherapy in Advanced Biliary Tract Cancer.Current oncology (Toronto, Ont.) · 2024Review
- Article
- Expression Profile of KRAS and p16 in Periampullary Cancer.Indian journal of surgical oncology · 2024Article
- Ampullary Adenocarcinoma: A Review of the Mutational Landscape and Implications for Treatment.Cancers · 2023Review
- [Treatment of Ampullary Adenocarcinoma].The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi · 2023Review
- Review
- Advances in medical treatment of advanced hepatobiliary and pancreatic cancer in 2022.Cancer innovation · 2023Review
- Ampulla of Vater carcinoma: advancement in the relationships between histological subtypes, molecular features, and clinical outcomes.Frontiers in oncology · 2023Review
- Optimizing Patient Pathways in Advanced Biliary Tract Cancers: Recent Advances and a French Perspective.Targeted oncology · 2023Review
- Ampullary carcinoma of the duodenum: current clinical issues and genomic overview.Surgery today · 2022Review
- Addition of trastuzumab emtansine (T-DM1) in a human epidermal growth factor receptor 2-overexpressed metastatic carcinoma of the gallbladder patient to enhance survival: A case study.SAGE open medical case reports · 2022Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The biological relevance of histological subtyping of ampullary carcinoma into intestinal vs pancreaticobiliary types remains to be determined. In an effort to molecularly profile these subtypes of ampullary carcinomas, we conducted a two-phase study. In the discovery phase, we identified 18 pancreatobiliary-type ampullary carcinomas and 14 intestinal-type ampullary carcinomas using stringent pathologic criteria and performed next-generation sequencing targeting 279 cancer-associated genes on these tumors. Although the results showed overlapping of genomic alterations between the two subtypes, trends including more frequent KRAS alterations in pancreatobiliary-type ampullary carcinoma (61 vs 29%) and more frequent mutations in APC in intestinal-type ampullary carcinoma (43 vs 17%) were observed. Of the entire cohort of 32 tumors, the most frequently mutated gene was TP53 (n=17); the most frequently amplified gene was ERBB2 (n=5); and the most frequently deleted gene was CDKN2A (n=6). In the second phase of the study, we aimed at validating our observation on ERBB2 and assessed ERBB2 amplification and protein overexpression in a series of 100 ampullary carcinomas. We found that (1) gene amplification and immunohistochemical overexpression of ERBB2 occurred in 13% of all ampullary carcinomas, therefore providing a potential target for anti-HER2 therapy in these tumors; (2) amplification and immunohistochemical expression correlated in all cases, thus indicating that immunohistochemistry could be used to screen tumors; and (3) none of the 14 ERBB2-amplified tumors harbored any downstream driver mutations in KRAS/NRAS, whereas 56% of the cases negative for ERBB2 amplification did, an observation clinically pertinent as downstream mutations may cause primary resistance to inhibition of EGFR family members.
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