Urine Biomarkers Sensitive, Specific for RCC Detection

Measurement of two biomarkers in urine indicates the presence of renal cell carcinoma

medwireNews: Urine levels of aquaporin-1 (AQP1) and perilipin-2 (PLIN2) are both sensitive and specific for the detection of renal cell carcinoma (RCC), suggests research published in JAMA Oncology.

“These tumor-specific proteins have high clinical validity and substantial potential as specific diagnostic and screening biomarkers for clear cell or papillary RCC and in the differential diagnosis of imaged renal masses”, say Jeremiah Morrissey, from Washington University in St Louis, Missouri, USA, and co-authors.

The team determined urine levels of the two biomarkers in 19 RCC patients and 80 healthy individuals, as well as a screening population of 720 patients who had undergone routine abdominal computed tomography (CT).

Median levels of AQP1 were significantly higher in RCC patients than in the healthy controls or the screening population, at 225.0 versus 1.1 and 0.5 ng/mg urine creatinine, respectively. This was also true for median levels of PLIN2, at 37.8 versus 3.1 and 0.0 absorbance units/mg creatinine, respectively.

In area under the receiver operating characteristic curve analysis, a urinary AQP1 cutoff of 7 ng/mg creatinine was 100% sensitive and 100% specific for the presence of RCC in patients versus healthy individuals.

And a urinary PLIN2 cutoff of 14 absorbance units/mg creatinine was 100% sensitive and 91% specific for the identification of RCC patients versus the healthy controls.

Three patients in the screening group were found to have a previously undetected renal mass or RCC and these individuals had urinary AQP1 and PLIN2 levels suggestive of RCC. Small, low-grade clear-cell RCCs were confirmed in two patients and the third died before diagnosis was made.

A further 16 patients in the screening group had renal lesions detected during CT that did not have malignant characteristics. These patients’ AQP1 and PLIN2 levels were below the cutoff levels for suspicion and significantly lower than those of the three patients with suspicious masses.

Moreover, their levels were “statistically indistinguishable” from the remainder of the screening patients with and without a history of cancer, the researchers say.

However, Brian Rini, from Cleveland Clinic Taussig Cancer Institute, and Steven Campbell, from Glickman Urological and Kidney Institute, both based in Ohio, USA, observe in an invited commentary that the biomarkers’ utility is limited as they do not indicate the “lethality” of any detected RCC.

Noting the risk of over-diagnosis and the low incidence of RCC in the general population, they emphasise the importance of a 100% specific test to avoid harm associated with false–positive tests, but suggest potential use of targeted screening for individuals at greater RCC risk, such as those with inherited syndromes or smokers.

Applying the biomarkers to patients with small renal masses detected during abdominal imaging may be “more immediately clinically relevant”, the commentators write, although hampered by the lack of correlation between biomarker levels and tumour grade.

They conclude: “This will require prospective study but is potentially valuable, especially ifAQP1 and PLIN2 measurement are able to obviate the need for biopsy or reduce the frequency of imaging in certain cohorts of patients.”


Morrissey JJ, Mellnick VM, Luo J, et al. Evaluation of urine aquaporin-1 and perilipin-2 concentrations as biomarkers to screen for renal cell carcinoma. A prospective cohort study. JAMA Oncol 2015; Advance online publication 19 March. doi:10.1001/jamaoncol.2015.0213

Rini BI, Campbell SC. Urinary biomarkers for the detection and management of localized renal cell carcinoma. JAMA Oncol 2015; Advance online publication 19 March. doi:10.1001/jamaoncol.2015.0262

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