Differential relationship between two hypoxia markers: HIF-1α and GLUT1 and classic prognostic factors in invasive breast carcinoma

Background: Tumor hypoxia is an adverse prognostic factor which promotes cancer aggressiveness and limits its radio- and chemosensitivity. The aim of our study was to explore the relationship between endogenous hypoxia markers and classic prognostic factors, including clinical stage and the expression of ER, PR, and HER2 in primary untreated breast carcinoma. Methods: A retrospective immunohistochemical analysis of archived tissue blocks collected from 153 women, who underwent total mastectomy and lymph node dissection, included the expression of two hypoxia-related proteins: HIF-1α and GLUT1. Results: GLUT1 labelling index (LI) showed a positive correlation with T stage (R = 0.18, p = 0.026) and HER2 status (R = 0.25, p = 0.002), and a negative correlation with the expression of ER (R = −0.19, p = 0.017) and PR (R = −0.17, p = 0.032). HIF-1α LI showed a positive correlation with ER expression (R = 0.16, p = 0.045). In the multivariate regression analysis, a different relationship between classic prognostic factors and the two tested hypoxia proteins was proven. Higher GLUT1 expression correlated with ER and PR negativity (p = 0.02 and p = 0.01, respectively) as well as with higher expression of HER2 (p = 0.04). HIF-1α showed no association with PR and HER2, but a positive correlation with ER (p = 0.02). Neither of the hypoxia proteins was associated with a tumor grade. Only one clinical feature, T stage, correlated with both of the hypoxia markers: positively with GLUT1 (p = 0.049) and negatively with HIF-1α (p = 0.01) expression. Conclusions: In breast cancer, GLUT1 expression may be considered an additional prognostic factor which correlates with an adverse status of HER2 and hormonal receptors, and indicates a more hypoxic, radio- and chemotherapy refractory profile of carcinoma