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Published on: July 28, 2010
Lack of HER2 overexpression and amplification in small intestinal adenocarcinoma
Owen T M Chan1, Zong-Ming E Chen, Fai Chung
1Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Abstract:
HER2 overexpression and amplification have been studied as a therapeutic and prognostic target in a number of human cancers, including esophageal, gastric, and colorectal adenocarcinomas. However, HER2 status has not been well investigated in primary small intestinal adenocarcinoma, probably because of its rarity. In this study, we conducted immunohistochemical analysis and fluorescence in situ hybridization (FISH) for HER2 on 49 primary nonampullar small intestinal adenocarcinomas. The results showed a complete lack of HER2 protein expression in 47 cases (96%) by immunohistochemical analysis. Only 2 cases (4%) showed a 1+ staining pattern. No tumors exhibited 2+ or 3+ HER2 immunoreactivity. By FISH, none of the tumors, including those with 1+ HER2 immunoreactivity, exhibited HER2 gene amplification. These observations demonstrate that HER2 protein overexpression and gene amplification are infrequent events, if they occur at all, in small intestinal adenocarcinoma. Thus, routine immunohistochemical and/or FISH testing for HER2 for potential targeted anti-HER2 therapy may not be beneficial for patients with primary small intestinal adenocarcinoma.
Insights
HER2 protein overexpression and gene amplification are rare in small intestinal adenocarcinoma. Routine testing for HER2 is likely not beneficial for patients with this rare cancer.
Area of Science:
- Oncology
- Gastroenterology
- Molecular Diagnostics
Background:
- HER2 (Human Epidermal growth factor Receptor 2) is a validated therapeutic and prognostic target in various adenocarcinomas.
- Its role in primary small intestinal adenocarcinoma remains largely unexplored due to the rarity of this cancer type.
Purpose of the Study:
- To investigate the status of HER2 protein expression and gene amplification in primary nonampullar small intestinal adenocarcinomas.
- To determine the potential utility of HER2-targeted therapies in this patient population.
Main Methods:
- Immunohistochemical (IHC) analysis was performed on 49 primary nonampullar small intestinal adenocarcinomas to assess HER2 protein expression.
- Fluorescence in situ hybridization (FISH) was utilized to evaluate HER2 gene amplification status.
Main Results:
- A complete lack of HER2 protein expression was observed in 96% of tumors via IHC.
- Only 4% of tumors showed minimal HER2 protein expression (1+ staining); none exhibited 2+ or 3+ immunoreactivity.
- FISH analysis revealed no HER2 gene amplification in any of the studied tumors, including those with 1+ HER2 immunoreactivity.
Conclusions:
- HER2 protein overexpression and gene amplification are infrequent in primary small intestinal adenocarcinoma.
- Current HER2 testing methods (IHC and FISH) may not be beneficial for guiding anti-HER2 therapy decisions in patients with this malignancy.
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