Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are highly heterogeneous diseases with a variable patient prognosis. The current grading system of GEP-NENs is primarily based on the proliferation status of the tumors. While this grading has some prognostic value, it can be subjective, and variable between different centers. Thus, there is an urgent need to identify superior methods to stratify GEP-NENs.
In this study, first, we aim to construct a comprehensive tissue microarray (TMA) from archival tissue from patients with GEP-NENs. This TMA will include 600 samples, in duplicate, from GEP-NENs from various primary sites (pancreas, stomach, small intestine, colon, and rectum), as well as patients with disease recurrence, and metastasis. We foresee that this GEP-NEN-TMA will facilitate the discovery of better prognostic markers, a better understanding of the biology of NENs, and the identification of therapeutic vulnerabilities. Herein, we propose to examine the prognostic value of two molecular subtypes, MLP and YAP-OFF, that our groups and others have shown to be involved in the progression of NENs. Notably, these molecular subtypes are currently not used in clinical practice, and this will be the first study to examine their clinical utility. Incorporating molecular subtypes in diagnosing patients with NENs can lead to better classification and prognosis, patient-specific treatment, and improve quality of life and overall survival.