Hypoxia-Regulated Proteins: Expression in Endometrial Cancer and Their Association with Clinicopathologic Features

Abstract

Background: Hypoxia-regulated proteins (HIF-1 alpha and GLUT-1) have been identified as prognostic markers in various cancers; however, their role in endometrial cancer remains unclear. This study aimed to evaluate HIF-1 alpha and GLUT-1 expression in endometrial cancer and correlate their expression with clinicopathological features. Materials and Methods: A tissue microarray (TMA) was constructed using specimens from a retrospective cohort of 51 endometrial cancer patients who underwent hysterectomy at the Gyeongsang National University Hospital between 2002 and 2009. Clinicopathologic data were collected from electronic medical records, and HIF-1 alpha and GLUT-1 expressions were assessed in the tumor tissue. Results: GLUT-1 expression in endometrial cancer was categorized as mosaic, central, or diffuse. Most patients (56.0%) exhibited a central pattern, followed by diffuse (32.0%) and mosaic (12.0%) patterns. GLUT-1 expression was not significantly associated with histologic grade (p = 0.365). HIF-1 alpha expression in immune cells, but not tumor cells, was significantly associated with a higher histologic grade. A higher proportion of HIF-1 alpha-positive immune cells, using both thresholds (<= 1% vs. >1% and <= 5% vs. >5%), was significantly associated with higher histologic grade (p = 0.032 and p = 0.048, respectively). In addition, a higher proportion of HIF-1 alpha-positive immune cells was significantly associated with a diffuse GLUT-1 expression pattern using >5% as a threshold. There were no significant differences in the proportion of HIF-1 alpha-positive immune cells between groups stratified by age, tumor size, or invasion depth, regardless of whether the 1% or 5% threshold for HIF-1 alpha positivity was used. Conclusions: A higher proportion of HIF-1 alpha-positive immune cells is associated with endometrial cancers with higher histologic grade and diffuse GLUT1 expression patterns. These findings suggest a potential role for HIF-1 alpha as a prognostic marker and highlight the need for further studies into the role of HIF-1 alpha in the tumor microenvironment.