From Initial Description by Wermer to Present-Day MEN1: What have We Learned?

Abstract

Introduction: Pancreas, parathyroid, and pituitary, are referred to as the "3 Ps" of MEN1. The time has come to move beyond those Ps and begin to discuss (1) prediction, (2) pausing progression, and (3) prevention of MEN1.

Methods: In preparation for the International Association of Endocrine Surgeons State of the Art address, updates and uncertainties of MEN were reviewed. This included a detailed examination of the MEN1 gene and the library of implicated mutations, exon sequencing databases and cell cycle pathways. Therapeutic options including radiofrequency ablation, systemic therapy, peptide receptor radionuclide therapy, immune checkpoint inhibitor mechanisms and preimplantation genetic testing were described.

Results: Several key points included mutations in exon 2 are suspected of being associated with a higher rate of distant metastases, a higher rate of PNET development, and more aggressive disease. The suggestion that missense mutations involving loss of interaction with CHES1 (associated with DNA repair) correlates with more aggressive disease and is more closely associated with death related to PNET than to death from other causes was mentioned. For advanced NETs, optimism for agents under study include lanreotide, a long-acting somatostatin analog, and everolimus (Afinitor), a mammalian target of rapamycin (mTOR) inhibitor. The NETest shows the potential value of being a multidimensional tumor marker for response to therapy. Preimplantation genetic diagnosis (PGD) is applicable.

Conclusion: Adjunct modalities and determination of the effect of therapy for MEN1 is needed. Prediction through early detection of aggressive disease is an idea worth spreading. We are called us to engage with our patients about prevention, the only true cure.