GLUT-1 expression in ovarian carcinoma - Association with survival and response to chemotherapy

BACKGROUND. Cancer cell growth is an energy-related process supported by an increased glucose metabolism. The objective of this study was to investiga te the association of GLUT-1 with response to chemotherapy and outcome in p atients with ovarian carcinoma. METHODS. Histologic sections of formalin fixed, paraffin embedded specimens from 113 primary ovarian carcinomas were stained for GLUT-1 by using polyc lonal GLUT-1 antibody (Dako Co., Carpinteria, CA) and the labeled streptavi din biotin procedure, Intensity of GLUT-1 staining was compared with diseas e free survival (DFS), chemotherapy response, and other clinicopathologic c haracteristics. RESULTS. GLUT-1 cytoplasmic membrane staining was observed in 89 of 104 (85 .6%) malignant tumors. Poorly differentiated tumors showed a trend to overe xpress the GLUT-1 protein compared with the more differentiated counterpart s (27.6% vs. 8.7%; P = 0.08). Patients who experienced a complete clinical response to chemotherapy were more frequently GLUT-1 positive than GLUT-1 n egative (80% vs. 51.5%; P 0.036). In multivariate analysis of advanced stag e disease, residual tumor (P 0.0001) and high GLUT-1 expression levels (P = 0.028) were the only independent variables that maintained a significant a ssociation with response to chemotherapy (P = 0.0001; chi-square = 38.13). In the subgroup of Stage III-IV (International Federation of Gynecology and Obstetrics patients showing a complete clinical response, GLUT-1 overexpre ssion was associated vith a shorter DFS. The median time to progression was 30 months in GLUT-1 strongly positive cases (> 50% of cancer cells positiv e) versus 60 months in GLUT-1 weakly positive cases (less than or equal to 50% of cancer cells positive; P = 0.024). CONCLUSIONS. GLUT-1 status is an independent prognostic factor of response to chemotherapy in advanced stage ovarian carcinoma. Moreover, patients ove rexpressing GLUT-1 show a significantly shorter DFS. These results suggest that the assessment of GLUT-1 status may provide clinically useful prognost ic information inpatients with ovarian carcinoma. (C) 2001 American Cancer Society.