Measurement of urinary canine S100A8/A9 and S100A12 concentrations as candidate biomarkers of lower urinary tract neoplasia in dogs

Members of the S100 family of calcium-binding proteins (S100A8, A9, and A12; calgranulins) have been associated with inflammation and cancer in human beings. Proteins S100A8 and A9 were overexpressed in human patients with transitional cell carcinoma (TCC) and prostate carcinoma (PCA), suggesting their potential as biomarkers for diagnosing and/or predicting the progression of such neoplasms. Calgranulins have not been studied in dogs with TCC or PCA. Established in-house immunoassays were validated and found suitable for measuring S100A8/A9 and S100A12 in canine urine samples to allow the study of the role of these biomarkers in dogs with TCC or PCA. Urinary calgranulin concentrations were not affected by blood contamination (e.g., due to cystocentesis), and should be normalized against urine specific gravity or urinary creatinine concentration. Urinary calgranulin concentrations were significantly increased in 11 dogs with TCC or PCA (untreated) compared to 42 healthy dogs, and the ratio between S100A8/A9 and S100A12 was significantly higher in 11 dogs with TCC or PCA than in 10 dogs diagnosed with a urinary tract infection, suggesting that calgranulins are potential biomarkers for TCC or PCA in canine patients. The clinical utility of measuring urinary calgranulins in dogs with suspected TCC or PCA warrants further investigation.