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

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Abstract

Purpose

To evaluate 18F-fluorodeoxyglucose (FDG) uptake to predict the malignant nature and analyze the correlation between FDG uptake and expression of glucose transporter 1 (Glut-1) and hexokinase II (HK-II) in thymic epithelial tumors.

Materials and methods

Eleven patients with a thymic epithelial tumor who underwent FDG PET/CT before therapy were reviewed. The thymic tumors were classified by the WHO histological classification and Masaoka clinical staging. Comparison of maximum standardized uptake value (SUVmax) of the lesion was made between the low-risk (Type A, AB and B1) and high-risk {Type B2, B3 and C (thymic cancer)} groups and among clinical stages. Expression of Glut-1 and HK-II was analyzed immunohistochemically.

Results

All 11 tumors showed FDG uptake visually. SUVmax was significantly higher in the high-risk group (n = 5, 5.24 ± 2.44) than the low-risk group (n = 6, 3.05 ± 0.55) (P = 0.008). Staining scores of both Glut-1 and HK-II were significantly higher in the high-risk group than in the low-risk group (Glut1: P = 0.034 and HK-II: P = 0.036). There were no significant differences in SUVmax (P = 0.11), Glut-1 (P = 0.35) and HK-II scores (P = 0.29) among clinical stages. SUVmax was significantly correlated to each of the staining scores of Glut-1 (ρ = 0.68, P = 0.031) and HK-II (ρ = 0.72, P = 0.024).

Conclusion

These preliminary results support the previously published view that SUVmax may be useful to predict the malignant nature of thymic epitherial tumors and suggest that the degree of FDG uptake in the thymic epitherial tumors is closely related to the amount of Glut-1 and HK-II in the tumor.

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.

Section snippets

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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