¹⁸F-FES and ¹⁸F-FDG PET for Differential Diagnosis and Quantitative Evaluation of Mesenchymal Uterine Tumors: Correlation with Immunohistochemical Analysis

Abstract

The aim of this study was to investigate the relationship between the tumor uptake of 16a-18 F-fluoro-17b-estradiol ( 18 F-FES) and 18 F-FDG using PET and expressions of sex hormone receptors, such as estrogen receptor (ER), as well as glucose transporter 1 (GLUT-1) and Ki-67 analyzed by the immunohistochemistry method in mesenchymal uterine tumors. Methods: Forty-seven patients with mesenchymal uterine tumors were studied with 18 F-FES and 18 F-FDG PET. Postoperative pathologic diagnosis revealed 33 uterine leiomyomas and 14 uterine sarcomas. Tissue samples were assayed for expression of ERa, ERb, progesterone receptor (PR), PR-B, GLUT-1, and Ki-67 by an immunohistochemistry method. Standardized uptake values (SUVs) for 18 F-FES and 18 F-FDG were compared with the semiquantitative immunoreactive score (0-12) and quantitative labeling index (LI) for Ki-67 in immunohistochemistry. Results: 18 F-FES uptake was significantly lower (P , 0.001) and the 18 F-FDG uptake and SUV ratio of 18 F-FDG to 18 F-FES ( 18 F-FDG/ 18 F-FES ratio) (P , 0.005 and P , 0.001, respectively) were significantly higher in uterine sarcomas than in leiomyomas. Immunohistochemistry analysis showed significantly higher expressions of ERa, PR, and PR-B in uterine leiomyomas than in sarcomas. The Ki-67 LI was significantly greater in uterine sarcomas than in leiomyomas. Correlation analysis for all tumors showed positive correlations between 18 F-FES SUV and immunohistochemistry scores of ERa, PR (P , 0.001), and PR-B (P , 0.005) as well as between 18 F-FDG SUV and GLUT-1 and Ki-67 (P , 0.001). However, the 18 F-FDG/ 18 F-FES ratio showed significantly negative correlations with ERa, PR (P , 0.001), and PR-B (P , 0.005) and a positive correlation with Ki-67 LI (P , 0.001). In uterine sarcomas, ERa and 18 F-FES SUV showed a positive correlation (P , 0.001) in a low SUV range, and the 18 F-FDG/ 18 F-FES ratio showed positive correlations with ERb and GLUT-1 expression (P , 0.005). Conclusion: 18 F-FES and 18 F-FDG PET showed correlations between tracer uptake and expressions of sex hormone receptors, GLUT-1, and Ki-67 in mesenchymal uterine tumors. The 18 F-FDG/ 18 F-FES ratio was correlated with Ki-67, GLUT-1, and ERb in uterine sarcoma. Functional PET imaging and PET parameters would be useful noninvasive biomarkers for the assessment of tumor hormone receptor expression, glucose metabolism, and proliferation and for differential diagnosis of uterine leiomyoma and sarcoma.

Radiopharmaceuticals as probes to characterize tumour tissue

“…The ER-specific tracer 18 F-FES has been used to characterize breast and uterine tumours with high sensitivity for noninvasive reporting of ER status [35,36,108]. Tsujikawa et al showed that 18 F-FES uptake in breast cancer patients is positively correlated with expression of ERα while 18 F-FDG uptake as expected failed to correlate with immunohistochemical scoring [35].…”

18F-Fluoroestradiol PET: Current Status and Potential Future Clinical Applications

“…In turn, highgrade carcinomas displayed higher 18 F-FDG-to-18 F-FES uptake ratios than did low-grade endometrial carcinomas. 18 F-FES PET also has potential to differentiate benign uterine leiomyomas from malignant uterine sarcomas on the basis of 18 F-FES uptake and 18 F-FDG-to-18 F-FES uptake ratio (47,48). Differentiation of sarcoma from leiomyoma can often be difficult with MRI (49), and 18 F-FDG PET findings can be equivocal (50).…”

“…Differentiation of sarcoma from leiomyoma can often be difficult with MRI (49), and 18 F-FDG PET findings can be equivocal (50). Similar to endometrial pathologies, lower 18 F-FES uptake and a higher 18 F-FDG-to-18 F-FES uptake ratio have been associated with malignant sarcomas (47,48). Given the substantial management and prognostic differences between the two entities, 18 F-FES PET can potentially play a role in risk stratification of indeterminate uterine masses.…”

Diagnostic imaging using positron emission tomography for gynecological malignancy

“…117,118 F-FES could provide better diagnostic value for differentiating between benign leiomyoma and uterine sarcoma. 123 In terms of the prognostic role of 18 F-FDG PET/CT, limited information is available. 124 Uterine sarcoma tends to have a huge solid structure with internal heterogeneity, and parameters to evaluate the entire tumor such as MTV or TLG might be more useful than local parameters such as SUVmax.…”