Abstract
The aim of this study was to investigate the expression of glutamine-metabolism-related proteins according to the histologic grade of phyllodes tumors (PTs) and to assess its clinical implication. We generated tissue microarrays of 224 PTs and performed immunohistochemical staining and western blot analysis of glutamine-metabolism-related molecules, including GLS1, GDH, and ASCT2. The associations between immunohistochemical results and clinicopathologic parameters were evaluated. The expression of GLS1 (p < 0.001), GDH (p < 0.001), and ASCT2 (p = 0.005) in stromal components significantly increased with worsening PT histological grade. GDH expression in epithelial components significantly increased in high-grade PT (p = 0.026). In western blot, stromal expression of GLS1, GDH, and ASCT2 increased as histologic grade increased. By univariate analysis, stromal GLS1 expression (p = 0.022) and stromal GDH expression (p = 0.009) were independent predictors of shorter DFS. Stromal GLS1 expression (p < 0.001) and stromal GDH expression (p < 0.001) were independent predictors of shorter OS. This study demonstrated that the stromal expression of the glutamine-metabolism-related proteins GLS1, GDH, ASCT2 increases with worsening histological PT grade.
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