Urine aquaporin 1 and perilipin 2 differentiate renal carcinomas from other imaged renal masses and bladder and prostate cancer

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.

Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Relative concentrations (normalized to urine creatinine concentration) of AQP1 (A) and PLIN2 (B) in the urine of patients with clear cell and papillary kidney cancers, all 26 control patients, and patients with an angiomyolipomas, chromophobe kidney cancer or an oncocytoma. Box plots show the median along with the 1st and 3rd quartile. (+) outlier > 1.5 and < 3 of the interquartile range. (*) outlier > 3 of the interquartile range. The median urine AQP1 and PLIN2 concentrations are significantly greater in RCC patients compared to the controls or other patient groups (P<0.001 for both, Kruskal-Wallis test with Bonferroni correction). The median and 1st/3rd quartile for urine PLIN2 of patients with an angiomyolipoma were significantly greater than that of controls (P<.001) or patients with oncocytoma (P<.001) (Kruskal-Wallis test). The insert shows ROC plots comparing the AQP1 or PLIN2 concentrations of the patients with RCC to that of all patients with AMLs, chromophobes and oncocytomas. The area under the ROC curves are 1.00 for Figures 1A and 0.99 for Figure 1B.

Figure 2

Relative concentrations (normalized to urine creatinine concentration) of AQP1 (A) and PLIN2 (B) in the urine of patients with clear cell and papillary kidney cancers, all 26 control patients, and patients with bladder or prostate cancer. Box plots show the median along with the 1st and 3rd quartile. (+) outlier > 1.5 and < 3 of the interquartile range. (*) outlier > 3 of the interquartile range. The median urine AQP1 and PLIN2 concentrations are significantly greater in RCC patients compared to the controls, and the patients with either bladder or prostate cancer (P<.01 for both, Kruskal-Wallis test). The insert shows ROC plots comparing the AQP1 or PLIN2 concentrations of the patients with RCC to that of all patients with bladder or prostate cancers. The area under the ROC curves is 1.00 each for Figures 2A and 2B.