Linked Hexokinase and Glucose-6-Phosphatase Activities Reflect Grade of Ovarian Malignancy

Birgitte Brinkmann Olsen, Albert Gjedde, Mie Holm Vilstrup, Iben Birgit Gade Johnsen, Gudrun Neumann, Drew Avedis Torigian, Abass Alavi, Poul Flemming Høilund-Carlsen

Malignant cells exhibit increased rates of aerobic glycolysis. Here, we tested whether the accumulation of fluoro-deoxyglucose-6-phosphate (FDG6P) in ovarian cancers of differential malignancy reflects inversely correlated elevations of hexokinase (HK) and glucose-6-phosphatase (G6Pase) activities. Twenty-nine women with suspected ovarian cancer had positron emission tomography (PET) prior to surgery. From fresh-frozen tissue, we determined the activities of HK and G6Pase, and from the PET images, we determined the tumor maximum standardized uptake value (SUVmax) of 2-deoxy-2-[18F]fluoro-D-glucose. The SUVmax of malignant lesions significantly exceeded the SUVmax of benign (p < 0.005) and borderline lesions (p < 0.0005) that did not differ significantly. We found no significant correlation between measured HK or G6Pase activities and histological tumor type or SUVmax except that G6Pase activities were higher in malignant than borderline lesions (p < 0.05). Measured HK and G6Pase activities correlated inversely (p < 0.05). The slopes from the regression lines of the three correlations yielded positively correlated abscissa and ordinate intercepts, designated HKmax and G6Pasemax, respectively (r = 0.67, p < 0.0001). The positive correlations between the abscissa and ordinate intercepts with SUVmax had regression coefficients of r = 0.44, p < 0.05; and r = 0.39, p < 0.05, respectively. The results distinguished two ovarian cancer phenotypes, one with elevated HK activity and low G6Pase activity, and another with the opposite characteristics.