The expression of metabolism-related proteins in phyllodes tumors

The purpose of this study was to investigate the association between the expression of hypoxia-inducible factor (HIF)-1 alpha, insulin-like growth factor (IGF)-1, glucose transporter 1 (Glut-1), carbonic anhydrase IX (CAIX), and monocarboxylate transporter (MCT)4, which are metabolism-related proteins in phyllodes tumors (PTs), and clinicopathologic factors and its implication. We used tissue microarrays to analyze 207 PTs and performed immunohistochemical staining against the glycolysis-related molecules HIF-1 alpha, IGF-1, Glut-1, CAIX, and MCT4. We then compared the immunohistochemical results and clinicopathologic parameters. The expressions of HIF-1 alpha, Glut-1, CAIX, and MCT4 in the stromal component of PTs increased (P = 0.019, P < 0.001, P = 0.045, and P < 0.001, respectively) with increasing tumor grade. According to univariate analysis, factors associated with shorter disease-free survival were Glut-1 expression (P = 0.001) and MCT4 expression (P < 0.001) in the stromal component, and the factors associated with shorter overall survival were IGF-1 expression (P = 0.012), Glut-1 expression (P < 0.001), CAIX expression (P = 0.039), and MCT4 expression (P < 0.001) in the stromal component. Our investigation of stromal expression of the metabolism-related proteins HIF-1 alpha, IGF-1, Glut-1, CAIX, and MCT4 revealed that, as the PT grade increased, the stromal expression of HIF-1 alpha, Glut-1, CAIX, and MCT4 significantly increased. This result suggested that increasing PT grade is associated with increased glycolysis in the stromal component.