MEN1-Related Neuroendocrine Tumors Show c-MET Overexpression.

Abstract

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.