Prognostic Significance of C-MYC and EGFR Overexpression in Gastrointestinal Stromal Tumors: An Immunohistochemical Study

Abstract

Introduction: In addition to mutations in KIT and PDGFRA, many other genetic alterations have been described in gastrointestinal stromal tumors (GISTs), including amplifications of C-MYC and EGFR, which are often associated with increased protein expression. The main of this study was to investigate the prognostic significance of C-MYC and EGFR expression in GISTs using immunohistochemistry (IHC).

Methods: We collected all GIST cases over a 16-year period. These cases were tested using antibodies against C-MYC (Leica, clone EP121) and EGFR (Leica, clone 113). C-MYC staining was assessed using the H-score method for nuclear, cytoplasmic, and combined staining. For EGFR staining (either cytoplasmic or nuclear), the intensity was graded as follows: 0 (no staining), 1 (weak staining), 2 (moderate staining), and 3 (strong staining). The percentage of positive cells was evaluated using a semiquantitative approach. Statistical analysis was performed using SPSS24.

Results: A total of 37 cases were included in our study. Nuclear expression of C-MYC was observed in 43% of the cases, with a high H-score in 43%. A statistically significant association was found between a high nuclear H-score for C-MYC and mitotic rate (P=0.046), as well as a high Ki-67 proliferation rate (P=0.046). However, no statistically significant associations were identified between the nuclear H-score of C-MYC and other clinical, pathologic, or survival data. Cytoplasmic expression of C-MYC was noted in 22% of cases, but no significant correlations were found with the clinicopathological data. EGFR staining was observed in 86% of cases, with a high score of 51%. EGFR expression was significantly associated with the mitotic index (P=0.012) and Ki-67 proliferation rate (P=0.046).

Conclusions: Our findings suggest that both C-MYC and EGFR may be overexpressed and/or amplified in GISTs, indicating their potential prognostic role. This could also pave the way for therapeutic strategies targeting these proteins.