Stromal Immune Contexture Predicts Disease-Free Survival in Gastro-Entero-Pancreatic Neuroendocrine Neoplasms (GEP-NENs)

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Introduction: Stromal Immune Contexture (SIC) helps predict prognosis in solid Tumors (T) but has been poorly investigated in gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs). We tested whether GEP-NENs profiling for adaptive immunity-related SIC markers, as well as inflammatory (COX2),EMT [Beta-catenin (B-cat)] and oncogenic pathway signaling (pS6) markers,could improve Ki67 and/or MO-based prediction of OS and DFS.

Aim(s): To explore Immune Contexture role in NEN prognosis.

Materials and methods: Surgical specimens from 314 GEP-NENs were analyzed for the following markers: MO (well vs poorly-differentiated T);Ki67;CD3,CD4,CD8,PD-1,PD-L1,HLA-I and HLA-DR by immunohistochemistry;B-Cat,COX2 and pS6. Each marker was independently evaluated in (T) and stroma (S) and SIC variables were combined to construct OS and DFS prognostic indices (PIs). PIs, primary tumor site, nuclear B-Cat, MO and Ki67 were used as continuous variable in a multivariable Cox analysis, and variable selection was based on Akaike Information Criterion (AIC). Two nomograms for predicting 5-year OS or DFS were generated based on selected variables. PIs and nomograms were also tested on 36 external GEP-NENs.

Conference: 15th Annual ENETSConcerence (2018)

Presenting Author: Milione M

Authors: Milione M, Miceli R, Pellegrinelli A, Spaggiari P, Tagliabue G,

Keywords: Neuroendocrine, Ki-67, Morphology, Immune contexture, PDL1, Beta-Catenin,