Longxiyu Meng1, Shun Zhang1,2, Jie Gao1, Qinfeng Xu3, Yao Fu4, Yi-Hua Zhou5, Feng Wang6, Hongqian Guo7,8. 1. Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Institute of Urology, Nanjing University, 321 Zhongshan Rd, Nanjing, Jiangsu, China. 2. Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, 321 Zhongshan Rd, Nanjing, 210008, Jiangsu, China. 3. Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Rd, Nanjing, Jiangsu, China. 4. Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Rd, Nanjing, Jiangsu, China. 5. Departments of Laboratory Medicine and Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Rd, Nanjing, Jiangsu, China. zgr03summer@126.com. 6. Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Rd, Nanjing, Jiangsu, China. fengwangcn@hotmail.com. 7. Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Institute of Urology, Nanjing University, 321 Zhongshan Rd, Nanjing, Jiangsu, China. dr.ghq@nju.edu.cn. 8. Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, 321 Zhongshan Rd, Nanjing, 210008, Jiangsu, China. dr.ghq@nju.edu.cn.
Abstract
OBJECTIVE: To evaluate the efficacy of parameters derived from [68Ga]Ga-PSMA-11 PET/CT images in predicting pathological HIF-2α expression in primary tumors among patients with renal cell carcinoma (RCC). METHODS: Fifty-three RCC patients with preoperative [68Ga]Ga-PSMA-11 PET/CT scans and complete surgical specimens were retrospectively enrolled in this study. Radiographic parameters were obtained from PET/CT images, and immunohistochemistry was used to measure the expression of HIF-2α and PSMA. Continuous variables and categorical variables were analyzed by the Mann-Whitney U test and chi-square test, respectively. ROC analysis was used to test the efficacy of several preoperative parameters in identifying pathological HIF-2α expression. Univariable logistic regression analyses were performed for significant parameters to predict pathological HIF-2α expression in RCC. RESULTS: Of the 53 tumors, 29 (54.7%) had high expression of HIF-2α. The SUVmax was significantly different in the HIF-2α expression subgroups (p < 0.001). SUVmax emerged as the most significant parameter to differentiate HIF-2α expression subgroups (high vs. low), with the AUC of 0.93 (95% CI 0.85-1.00, p < 0.001), sensitivity of 90%, and specificity of 88%. Furthermore, SUVmax was confirmed as the most significant predictor of HIF-2α expression level by univariable logistic regression model analysis (odds ratio 1.39, 95% CI 1.17-1.65, p < 0.001). Consistent with the radiographic results of [68Ga]Ga-PSMA-11 PET/CT, the staining intensity of pathological PSMA was significantly higher in HIF-2α-high-expressing tumors (p = 0.003). CONCLUSIONS: [68Ga]Ga-PSMA-11 PET/CT was superior in identifying pathological HIF-2α expression in primary tumors of RCC patients, demonstrating its potential application in predicting responses to HIF-2α antagonists. KEY POINTS: • [68Ga]Ga-PSMA-11 PET/CT could potentially predict the HIF-2α expression of primary tumors among patients with RCC. • SUVmaxof [68Ga]Ga-PSMA-11 PET/CT was the most significant predictor of HIF-2α expression level. • This probability could help predict the therapeutic response of patients with RCC to HIF-2α antagonists.
OBJECTIVE: To evaluate the efficacy of parameters derived from [68Ga]Ga-PSMA-11 PET/CT images in predicting pathological HIF-2α expression in primary tumors among patients with renal cell carcinoma (RCC). METHODS: Fifty-three RCC patients with preoperative [68Ga]Ga-PSMA-11 PET/CT scans and complete surgical specimens were retrospectively enrolled in this study. Radiographic parameters were obtained from PET/CT images, and immunohistochemistry was used to measure the expression of HIF-2α and PSMA. Continuous variables and categorical variables were analyzed by the Mann-Whitney U test and chi-square test, respectively. ROC analysis was used to test the efficacy of several preoperative parameters in identifying pathological HIF-2α expression. Univariable logistic regression analyses were performed for significant parameters to predict pathological HIF-2α expression in RCC. RESULTS: Of the 53 tumors, 29 (54.7%) had high expression of HIF-2α. The SUVmax was significantly different in the HIF-2α expression subgroups (p < 0.001). SUVmax emerged as the most significant parameter to differentiate HIF-2α expression subgroups (high vs. low), with the AUC of 0.93 (95% CI 0.85-1.00, p < 0.001), sensitivity of 90%, and specificity of 88%. Furthermore, SUVmax was confirmed as the most significant predictor of HIF-2α expression level by univariable logistic regression model analysis (odds ratio 1.39, 95% CI 1.17-1.65, p < 0.001). Consistent with the radiographic results of [68Ga]Ga-PSMA-11 PET/CT, the staining intensity of pathological PSMA was significantly higher in HIF-2α-high-expressing tumors (p = 0.003). CONCLUSIONS: [68Ga]Ga-PSMA-11 PET/CT was superior in identifying pathological HIF-2α expression in primary tumors of RCC patients, demonstrating its potential application in predicting responses to HIF-2α antagonists. KEY POINTS: • [68Ga]Ga-PSMA-11 PET/CT could potentially predict the HIF-2α expression of primary tumors among patients with RCC. • SUVmaxof [68Ga]Ga-PSMA-11 PET/CT was the most significant predictor of HIF-2α expression level. • This probability could help predict the therapeutic response of patients with RCC to HIF-2α antagonists.
Authors: Christophe Van de Wiele; Mike Sathekge; Bart de Spiegeleer; Pieter Jan De Jonghe; Philip R Debruyne; Marleen Borms; Laurence Beels; Alex Maes Journal: Histol Histopathol Date: 2020-04-13 Impact factor: 2.303