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

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Purpose: 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. Procedures: 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. Results: 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. Conclusions: The results distinguished two ovarian cancer phenotypes, one with elevated HK activity and low G6Pase activity, and another with the opposite characteristics.

OriginalsprogEngelsk
TidsskriftMolecular Imaging and Biology
Vol/bind21
Udgave nummer2
Sider (fra-til)375-381
ISSN1536-1632
DOI
StatusUdgivet - apr. 2019

Fingeraftryk

Glucose-6-Phosphatase
Hexokinase
Ovarian Neoplasms
Neoplasms
Fluorodeoxyglucose F18
Glycolysis

Citer dette

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title = "Linked Hexokinase and Glucose-6-Phosphatase Activities Reflect Grade of Ovarian Malignancy",
abstract = "Purpose: 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. Procedures: 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. Results: 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. Conclusions: The results distinguished two ovarian cancer phenotypes, one with elevated HK activity and low G6Pase activity, and another with the opposite characteristics.",
author = "Olsen, {Birgitte Brinkmann} and Albert Gjedde and Vilstrup, {Mie Holm} and Johnsen, {Iben Birgit Gade} and Gudrun Neumann and Torigian, {Drew Avedis} and Abass Alavi and H{\o}ilund-Carlsen, {Poul Flemming}",
year = "2019",
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doi = "10.1007/s11307-018-1247-2",
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journal = "Molecular Imaging and Biology",
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Linked Hexokinase and Glucose-6-Phosphatase Activities Reflect Grade of Ovarian Malignancy. / Olsen, Birgitte Brinkmann; Gjedde, Albert; Vilstrup, Mie Holm; Johnsen, Iben Birgit Gade; Neumann, Gudrun; Torigian, Drew Avedis; Alavi, Abass; Høilund-Carlsen, Poul Flemming.

I: Molecular Imaging and Biology, Bind 21, Nr. 2, 04.2019, s. 375-381.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Linked Hexokinase and Glucose-6-Phosphatase Activities Reflect Grade of Ovarian Malignancy

AU - Olsen, Birgitte Brinkmann

AU - Gjedde, Albert

AU - Vilstrup, Mie Holm

AU - Johnsen, Iben Birgit Gade

AU - Neumann, Gudrun

AU - Torigian, Drew Avedis

AU - Alavi, Abass

AU - Høilund-Carlsen, Poul Flemming

PY - 2019/4

Y1 - 2019/4

N2 - Purpose: 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. Procedures: 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. Results: 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. Conclusions: The results distinguished two ovarian cancer phenotypes, one with elevated HK activity and low G6Pase activity, and another with the opposite characteristics.

AB - Purpose: 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. Procedures: 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. Results: 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. Conclusions: The results distinguished two ovarian cancer phenotypes, one with elevated HK activity and low G6Pase activity, and another with the opposite characteristics.

U2 - 10.1007/s11307-018-1247-2

DO - 10.1007/s11307-018-1247-2

M3 - Journal article

VL - 21

SP - 375

EP - 381

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

SN - 1536-1632

IS - 2

ER -