MEN1-related Neuroendocrine Tumors show c-MET Overexpression

Context Approximately 50-70% of patients with multiple endocrine neoplasia type 1 (MEN1) die of duodenopancreatic neuroendocrine tumors (NETs). While c-MET inhibitors in combination with anti-VEGF 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 is lacking. Objective We sought to characterize c-MET expression in MEN1-related NETs and evaluate its association with clinicopathologic characteristics. Patients Forty-three tumors from twenty-two genetically confirmed patients with MEN1-related metastatic NETs were identified. Of these, 15/22 (68%) patients had distant metastases while remaining 7/22 had locoregional metastases. Results c-MET expression was assessed in these tumors via immunohistochemistry. 19/43 (44%) were primary tumors (duodenum, pancreas, stomach) while remaining were metastases. c-MET expression was scored as strongly positive in 3/43 (H score >50), weakly positive in 6/43 (H score: 10-50) and negative in 34/43 (H-score <10) tumors. All three tumors with strong positive c-MET expression were from patients with distinctly aggressive clinical course. The six tumors with weak positive c-MET expression were from patients with stable disease including four with distant metastases. Of the 13 patients with all tumors negative for c-MET expression, all but one 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.