18FDG PET for grading malignancy in thymic epithelial tumors: Significant differences in 18FDG uptake and expression of glucose transporter-1 and hexokinase II between low and high-risk tumors: Preliminary study
Introduction
Thymic epithelial tumors are the most frequent tumors of the anterosuperior mediastinum. In 1999, the World Health Organization (WHO) published its histological classification of thymic tumors [1]. Recently, it has been reported that the WHO histological classification reflects both the clinical and functional features of thymic epithelial tumors and is thus useful in clinical practice for both assessment and treatment [2], [3], [4]. It has been found that type A, AB, and B1 thymomas are less aggressive and have better prognosis than type B2, B3 and/or C (cancer) thymomas [2], [3], [4]. In addition, the WHO histological classification and Masaoka clinical staging have been reported to be independent prognostic factors of overall survival after complete resection [4].
18F-fluorodeoxyglucose positron emission tomography (FDG PET) can detect enhanced glycolysis of tumor cells and has been proven valuable in diagnosing, staging, detecting recurrences, and assessing response to therapy in a multitude of malignant disorders [5]. Increased glucose uptake is found in malignant tumors because of increased levels of both glucose transporters (Gluts) and intracellular enzymes such as hexokinase (HK) that promote glycolysis [6]. Cellular concentration of FDG in a tumor represents the glycolytic activity of viable tumor cells [6].
While the significance of FDG PET in thymic epithelial tumors has been reported in several studies [7], [8], [9], [10], [11], [12], [13], there is a limitation on evaluation of FDG uptake in different subgroups of thymic epithelial tumors based on the WHO classification with some conflicting results [10], [11], [12]. In addition, it appears that no studies have been done to assess expression of Gluts and HK in association with FDG uptake in thymic epithelial tumors.
The present study was performed to examine whether FDG PET has the potential to grade malignancy in thymic epithelial tumors, and to explore the association of FDG uptake with the expression of Glut-1 and HK-II in thymic epithelial tumors.
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Patients
This was a retrospective study of 11 patients (5 men and 6 women, mean age 55, age range; 41–71 years) with a histologically proven thymic epithelial tumor. They underwent whole-body FDG PET/CT before treatment from March 2007 to January 2009. Seven asymptomatic patients were discovered by a medical examination in which the chest X-ray film showed mediastinal widening or a mass. Three patients presented with chest pain and the remaining one patient presented signs of myasthenia gravis. Ten
Results
Table 1 shows characteristics of 11 thymic epitherial tumors. There were 6 (3 type A, 1 type AB and 2 type B1) tumors in the low-risk group and 5 (3 type B2, 1 type B3 and 1 type C) tumors in the high-risk group, and 2 patients in Stage I, 5 in Stage II, 3 in Stage III and 1 in Stage IVa.
All 11 tumors showed 18F-FDG uptake visually. The SUVmax was significantly higher in the high-risk group (mean ± SD: 5.24 ± 2.44, range: 3.9–9.6) than in the low-risk group (mean ± SD: 3.05 ± 0.55, range: 2.5–3.9) (P =
Discussion
To evaluate the FDG uptake to predict the malignant nature of thymic epithelial tumors, we first examined the relationships in SUVmax and FDG uptake pattern, morphological characteristics including tumor contour, shape and calcification between the low-risk and high-risk groups and among the clinical stages and between SUVmax and tumor size. Next we examined Glut-1 and HK-II expressions in thymomas and relationships with FDG SUVmax.
Conclusions
FDG uptake in thymic epithelial tumors showed a significant difference in SUVmax between the low and high-risk simplified WHO classification groups, and these preliminary results support the previously published view that SUVmax may be useful to predict the malignant nature of thymic epitherial tumors. The present preliminary study also demonstrates significant positive correlations between FDG SUVmax and each of Glut-1 and HK-II expressions, suggesting that the degree of FDG uptake in the
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2015, Biochemical and Biophysical Research CommunicationsIs <sup>18</sup>F-FDG PET useful in predicting the WHO grade of malignancy in thymic epithelial tumors? A meta-analysis
2014, Lung CancerCitation Excerpt :Only data about SUVmax were sufficient to perform a meta-analysis on the different glucose metabolism among the various risk classes of TETs. Eleven studies [36–46] provided sufficient data to calculate the pooled WMD of SUVmax among the various groups of TETs (Table 3). The WMD of SUVmax among high-risk and low-risk thymomas ranged from −0.9 to 4.3 with a pooled WMD of 1.2 (95%CI: 0.4 to 2) therefore a significant higher mean SUVmax in the group of high-risk thymomas compared to low-risk thymomas was found (Fig. 2).
Role of combined <sup>18</sup>F-FDG-PET/CT for predicting the WHO malignancy grade of thymic epithelial tumors: A multicenter analysis
2013, Lung CancerCitation Excerpt :In detail, Luzzi [14] evidenced a direct correlation of the SUVmax with the Masaoka stages (r = 0.83, p < 0.01) but at the same time no correlation was found among the SUVmax and the tumor-size (r = 0.26, p = 0.31). Only a marginally significant (p = 0.06) correlation between the SUVmax and the tumor-size was reported by Nakajo et al. [25]. From this perspective, the SUVmax/T-size index as a possible predictive factor of the grade of malignancy outlined in our report seems to overcome this bias, this parameter more accurately reflecting the “real” biological behavior of the tumor (SUVmax) in a (statistically significant) independent manner from the extension of the tumor itself.
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