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Published on: March 14, 2021
MEN1-Related Neuroendocrine Tumors Show c-MET Overexpression
Raisa Ghosh1, Dilara Akbulut2, William F Simonds1
1Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Context:
Approximately 50% to 70% of patients with multiple endocrine neoplasia type 1 (MEN1) die of duodenopancreatic neuroendocrine tumors (NETs). While c-MET inhibitors in combination with antivascular endothelial growth factor therapy have been shown to result in longer progression-free survival in patients with sporadic NETs, data regarding their efficacy in patients with MEN1-related NETs are lacking.
Objective:
We sought to characterize c-MET expression in MEN1-related NETs and evaluate its association with clinicopathologic characteristics.
Methods:
Forty-three tumors from 22 genetically confirmed patients with MEN1-related metastatic NETs were identified. Of these, 15 of 22 (68%) patients had distant metastases while the remaining 7 of 22 had locoregional metastases.
Results:
c-MET expression was assessed in these tumors via immunohistochemistry. A total of 19 of 43 (44%) were primary tumors (duodenum, pancreas, stomach) while the remaining were metastases. c-MET expression was scored as strongly positive in 3 of 43 (H-score >50), weakly positive in 6 of 43 (H-score: 10-50), and negative in 34 of 43 (H-score <10) tumors. All 3 tumors with strong positive c-MET expression were from patients with a distinctly aggressive clinical course. The 6 tumors with weakly positive c-MET expression were from patients with stable disease, including 4 with distant metastases. Of the 13 patients with all tumors negative for c-MET expression, all but 1 had stable disease. Age at initial NET diagnosis; tumor site, type or grade; number of sites of distant metastases; total number of surgeries for NETs; or the stability of overall tumor burden did not predict c-MET expression.
Conclusion:
Our findings suggest a role for c-MET inhibition in personalizing therapy for patients with MEN1-related NETs.
Insights
This study investigated c-MET expression in multiple endocrine neoplasia type 1 (MEN1) related neuroendocrine tumors (NETs). Positive c-MET expression correlated with aggressive disease, suggesting potential for targeted therapies.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Multiple endocrine neoplasia type 1 (MEN1) patients have high mortality from duodenopancreatic neuroendocrine tumors (NETs).
- Current treatments combining c-MET inhibitors and anti-VEGF show promise for sporadic NETs, but efficacy in MEN1-NETs is unknown.
Purpose of the Study:
- To characterize c-MET expression in MEN1-related NETs.
- To evaluate the association between c-MET expression and clinicopathologic features in MEN1-NETs.
Main Methods:
- Analysis of 43 tumors from 22 genetically confirmed MEN1 patients with metastatic NETs.
- Immunohistochemistry used to assess c-MET expression levels (negative, weak, strong).
- Correlation of c-MET expression with clinical data, including metastasis and disease course.
Main Results:
- c-MET expression was assessed in 43 MEN1-related NETs (primary and metastatic).
- Strong positive c-MET expression (3/43 tumors) was linked to aggressive clinical courses.
- Negative c-MET expression (34/43 tumors) was predominantly associated with stable disease.
Conclusions:
- c-MET expression patterns in MEN1-NETs correlate with disease behavior.
- Targeted c-MET inhibition may offer a personalized therapeutic strategy for MEN1-NET patients.
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