Analysis of MET and RET Expression in Patients with Pancreatic Neuroendocrine Tumors Receiving Everolimus


Introduction: Target therapy has improved the outcome of neuroendocrine tumors (NETs), but little is known about the strategies to overcome the acquired resistance. MET is considered one of the putative mechanisms of resistance. RET is also rearranged in some other endocrine tumors (like thyroid).

Aim(s): We performed an analysis of MET and RET expression in patients with metastatic pancreatic NETs receiving everolimus, before and after treatment, in order to investigate if MET or RET pathways activate as putative mechanisms of resistance to mTOR inhibitors. Other exploratory analyses have been performed.

Materials and methods: Liver biopsies from 10 patients before and after everolimus were collected. We used FISH for RET rearrangement and MET amplification and immunohistochemical (IHC) analysis for phospho-Met and PTEN protein expression. We addictionally speculate the role of PDL-1 IHC expression as putative predictive biomarker. A novel next generation sequencing (Oncomine™ Solid Tumour DNA) was used to detect the mutation of 22 genes: EGFR, ERBB2, ERB4, MET, FGFR1, FGFR2, FGFR3, DDR2, ALK, KRAS, NRAS, PIK3CA, BRAF, PTEN, MAP2K1, AKT1, TP53, STK11, CTNNB1, SMAD4, FBXW7, NOTHC1.

Conference: 15th Annual ENETSConcerence (2018)

Presenting Author:

Authors: Cella C, Barberis M, Spad F, Pisa E, Laffi A,

Keywords: Everolimus, MET, RET,

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