Jeremiah J Morrissey1, Jonathan Mobley2, R Sherburne Figenshau3, Joel Vetter2, Sam Bhayani3, Evan D Kharasch4. 1. Department of Anesthesiology, Division of Clinical and Translational Research, Washington University in St Louis, St Louis, MO; Siteman Cancer Center, Washington University in St Louis, St Louis, MO. Electronic address: morrisse@wustl.edu. 2. Department of Urology, Washington University in St Louis, St Louis, MO. 3. Siteman Cancer Center, Washington University in St Louis, St Louis, MO; Department of Urology, Washington University in St Louis, St Louis, MO. 4. Department of Anesthesiology, Division of Clinical and Translational Research, Washington University in St Louis, St Louis, MO; Siteman Cancer Center, Washington University in St Louis, St Louis, MO; Department of Biochemistry and Molecular Biophysics, Washington University in St Louis, St Louis, MO.
Abstract
OBJECTIVE: To evaluate the sensitivity and specificity of urine aquaporin 1 (AQP1) and perilipin 2 (PLIN2) concentrations to diagnose clear cell or papillary renal cell carcinoma (RCC) by comparing urine concentrations of these unique biomarkers in patients with RCC, noncancer renal masses, bladder cancer, and prostate cancer. METHODS: From February 1, 2012, through October 31, 2012, preoperative urine samples were obtained from patients with a presumptive diagnosis of RCC based on an imaged renal mass, prostate cancer, or transitional cell bladder cancer. Imaged renal masses were diagnosed postnephrectomy—as malignant or benign—by histology. Urine AQP1 and PLIN2 concentrations were measured by using a sensitive and specific Western blot and normalized to urine creatinine concentration. RESULTS: Median concentrations of urine AQP1 and PLIN2 in patients with clear cell and papillary RCC (n=47) were 29 and 36 relative absorbance units/mg urine creatinine, respectively. In contrast, median concentrations in patients with bladder cancer (n=22) and prostate cancer (n=27), patients with chromophobe tumors (n=7), and patients with benign renal oncocytomas (n=9) and angiomyolipomas (n=7) were all less than 10 relative absorbance units/mg urine creatinine (Kruskal-Wallis test, P<.001 vs RCC for both biomarkers) and comparable with those in healthy controls. The area under the receiver operating characteristic curve ranged from 0.99 to 1.00 for both biomarkers. CONCLUSION: These results support the specificity and sensitivity of urine AQP1 and PLIN2 concentrations for RCC. These novel tumor-specific proteins have high clinical validity and high potential as specific screening biomarkers for clear cell and papillary RCC as well as in the differential diagnosis of imaged renal masses. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00851994.
OBJECTIVE: To evaluate the sensitivity and specificity of urine aquaporin 1 (AQP1) and perilipin 2 (PLIN2) concentrations to diagnose clear cell or papillary renal cell carcinoma (RCC) by comparing urine concentrations of these unique biomarkers in patients with RCC, noncancer renal masses, bladder cancer, and prostate cancer. METHODS: From February 1, 2012, through October 31, 2012, preoperative urine samples were obtained from patients with a presumptive diagnosis of RCC based on an imaged renal mass, prostate cancer, or transitional cell bladder cancer. Imaged renal masses were diagnosed postnephrectomy—as malignant or benign—by histology. Urine AQP1 and PLIN2 concentrations were measured by using a sensitive and specific Western blot and normalized to urine creatinine concentration. RESULTS: Median concentrations of urine AQP1 and PLIN2 in patients with clear cell and papillary RCC (n=47) were 29 and 36 relative absorbance units/mg urine creatinine, respectively. In contrast, median concentrations in patients with bladder cancer (n=22) and prostate cancer (n=27), patients with chromophobe tumors (n=7), and patients with benign renal oncocytomas (n=9) and angiomyolipomas (n=7) were all less than 10 relative absorbance units/mg urine creatinine (Kruskal-Wallis test, P<.001 vs RCC for both biomarkers) and comparable with those in healthy controls. The area under the receiver operating characteristic curve ranged from 0.99 to 1.00 for both biomarkers. CONCLUSION: These results support the specificity and sensitivity of urine AQP1 and PLIN2 concentrations for RCC. These novel tumor-specific proteins have high clinical validity and high potential as specific screening biomarkers for clear cell and papillary RCC as well as in the differential diagnosis of imaged renal masses. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00851994.
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