Association of p16 Loss and EZH2 Overexpression with Clinicopathological Characteristics and Prognosis in Gastrointestinal Stromal Tumors

Abstract

AbstractAim: Gastrointestinal stromal tumors (GISTs) exhibit marked heterogeneous clinical behavior that is not fully captured by conventional risk classification systems. This study aimed to evaluate the prognostic significance of loss of p16 expression and EZH2 overexpression and their relationship with clinicopathological parameters in GIST.Methods: In this retrospective study, 113 GIST cases diagnosed at a single institution between 2016 and 2026 were evaluated. Expression of p16 and EZH2 was evaluated immunohistochemically and correlated with clinicopathological parameters and overall survival using Kaplan-Meier and Cox regression analyses.Results: p16 loss was detected in 34 cases (30.1%) and EZH2 overexpression in 12 cases (10.6%). Both markers were significantly correlated with high mitotic activity, tumor necrosis, metastasis, multifocality, a high AFIP risk category, and elevated Ki-67 proliferation index (p