Abstract
The accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) can be influenced by the increased glycolytic activity of inflammatory lesions. Here, using clinical data obtained from gynecological cancer patients, tumor samples and animal models, we investigate the impact of pretreatment tumor-related leukocytosis (TRL) on the diagnostic performance of 18F-FDG-PET/CT in detecting pelvic and paraaortic lymph node metastasis. We demonstrate that pretreatment TRL misleads 18F-FDG-PET/CT during lymph node staging in gynecological malignancies. In the mechanistic investigations, we show that the false-positive 18F-FDG-PET/CT result for detecting nodal metastasis can be reproduced in animal models of TRL-positive cancer bearing G-CSF expressing cervical cancer cells. We also show that increased 18F-FDG uptake in non-metastatic nodes can be explained by the MDSC-mediated premetastatic niche formation in which proinflammatory factors, such as S100A8 or S100A9, are abundantly expressed. Together, our results suggest that the MDSC-mediated premetastatic niche created in the lymph node of TRL-positive patients misleads 18F-FDG-PET/CT for detecting nodal metastasis.
Highlights
The accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-Positron emission tomography (PET)/Computed tomography (CT)) can be influenced by the increased glycolytic activity of inflammatory lesions
Using clinical data obtained from patients, we investigated the impact of pretreatment tumor-related leukocytosis (TRL) on the diagnostic performance of 18F-FDG-PET/CT in detecting pelvic and paraaortic lymph node metastasis in gynecological cancer patients
We previously demonstrated that increased granulopoiesis induced by tumor-derived G-CSF is responsible for the development of TRL21, and that the premetastatic niche created by G-CSF-induced myeloid-derived suppressor cells (MDSC) is responsible for the highly metastatic nature of TRL-positive uterine cervical and endometrial cancer[20]
Summary
The accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) can be influenced by the increased glycolytic activity of inflammatory lesions. Using clinical data obtained from gynecological cancer patients, tumor samples and animal models, we investigate the impact of pretreatment tumor-related leukocytosis (TRL) on the diagnostic performance of 18F-FDG-PET/CT in detecting pelvic and paraaortic lymph node metastasis. Our results suggest that the MDSC-mediated premetastatic niche created in the lymph node of TRL-positive patients misleads 18F-FDG-PET/CT for detecting nodal metastasis. Computed tomography (CT) and magnetic resonance imaging (MRI) have been widely used to assess lymph node metastases in patients with gynecological cancers Both techniques base the identification of metastatic nodes on node size measurements; a short-axis diameter greater than 10 mm is the most accepted criterion. Considering the proinflammatory nature of the premetastatic niche, theoretically, MDSC-mediated premetastatic niches in TRL-positive cancer patients may manifest as hypermetabolic lesions on 18F-FDG-PET/CT, which can cause falsepositive 18F-FDG-PET/CT results. The association between the presence of pretreatment TRL and the diagnostic performance of 18F-FDG-PET/CT during lymph node staging has yet to be investigated
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