Related Experiment Video
Updated: May 11, 2026
Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
Molecular alterations of EGFR in small intestinal adenocarcinoma
Yan Wang1, Cong-Qing Jiang, Jing Guan
1Department of Pathology, School of Basic Medical Science, Wuhan University, 185 Donghu Road, Wuchang District, 430071, Wuhan, China.
Background And Aims:
Molecular testing for epidermal growth factor receptor (EGFR) mutations has recently become a standard practice for the management of patients with non-squamous none small cell lung cancer. Primary small intestine adenocarcinoma (SIA) is an uncommon malignancy, and EGFR mutation in the cancer has not been well characterized due to its rarity.
Methods:
A micro-tissue array with 53 SIAs and 24 surgically resected primary non-ampullary SIAs were studied. EGFR mutations were analyzed by DNA sequencing in 24 cases with formalin-fixed paraffin-embedded blocks. All 77 cases were examined by immunohistochemistry (IHC) using antibodies specific for the EGFR E746-A750 deletion in exon 19 (DEL), L858R point mutation in exon 21 (L858R), and total EGFR. EGFR amplifications were detected by fluorescence in situ hybridization.
Results:
A positive reaction of DEL-specific, L858R-specific, and total EGFR antibodies was detected in seven (9.1%), 5 (6.5%) and 35 (45.5%) of 77 SIAs by IHC, respectively. Positive reaction of the three antibodies was not significantly correlated with patient's age, gender, differentiation, and stage. EGFR gene amplification was assayed in 77 SIAs in micro-tissue array. Of 24 SIA samples that had DNA sequencing, two (8.3%) harbored exon 19 deletion and one (4.2%) harbored L858R point mutation. Only one case with EGFR amplification and two cases with polysomy were shown.
Conclusions:
Our findings suggested that mutations and amplification in EGFR genes are minor events, and most of SIAs may be unsuitable to EGFR-TKIs treatment.
Insights
Epidermal growth factor receptor (EGFR) mutations are uncommon in small intestine adenocarcinoma (SIA). Most SIAs are likely unsuitable for EGFR-targeted therapies due to low mutation and amplification rates.
Area of Science:
- Oncology
- Molecular Diagnostics
- Gastrointestinal Cancer Research
Background:
- Epidermal growth factor receptor (EGFR) mutation testing is standard for non-squamous non-small cell lung cancer.
- Primary small intestine adenocarcinoma (SIA) is rare, and its EGFR mutation status is poorly understood.
Purpose of the Study:
- To characterize EGFR mutations and amplification in primary small intestine adenocarcinoma.
- To evaluate the potential suitability of SIA patients for EGFR-tyrosine kinase inhibitor (TKI) therapy.
Main Methods:
- Analyzed 77 primary small intestine adenocarcinomas using immunohistochemistry (IHC) for EGFR mutations (exon 19 deletion, L858R) and total EGFR.
- Performed DNA sequencing on 24 SIA cases for EGFR mutations.
- Assessed EGFR amplification using fluorescence in situ hybridization (FISH).
Main Results:
- IHC detected EGFR mutations in 9.1% (exon 19 deletion) and 6.5% (L858R) of SIAs.
- DNA sequencing confirmed exon 19 deletion in 8.3% and L858R in 4.2% of cases.
- EGFR gene amplification was rare, observed in only one case, with two cases showing polysomy.
Conclusions:
- EGFR mutations and amplification are infrequent events in primary small intestine adenocarcinoma.
- The low prevalence suggests most SIA patients are unlikely to benefit from EGFR-targeted therapies.
Related Concept Videos
02:38Mitogens and the Cell Cycle
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase