Proteomic assays for the detection of urothelial cancer

Bladder cancer is one of the most expensive cancers from diagnosis to death of the patient due to life-long surveillance involving upper tract imaging, urinary cytology, and cystoscopy. Cytology has been historically used in conjunction with cystoscopy to help detect disease that may be missed by routine cystoscopy (e.g., carcinoma in situ and upper tract disease). Urine cytology is highly cytopathologist dependent and has reasonable sensitivity for detecting high grade disease. However, its sensitivity drops precipitously with regard to well-differentiated low grade cancers. Intensive investigations have been undertaken using proteomics to find an alternative to cystoscopy and cytology. Urine proteomic markers currently evaluated critically in the literature include bladder tumor antigen, nuclear matrix protein 22, BLCA-4, hyaluronic acid, hyaluronidase, cytokeratin 8, cytokeratin 18, cytokeratin 19, tissue polypeptide antigen, and tissue polypeptide-specific antigen. Markers used as alternatives to cystoscopy must be accurate with high sensitivity and specificity, cost effective for life-long surveillance, and minimally invasive to minimize the burden to the patient. To date, no proteomic marker has been developed that can replace cystoscopy for the detection of bladder cancer. However, several urinary markers appear to have higher sensitivity albeit lower specificity than cytology and can be used to supplement cystoscopy. Some of those markers are herein described in this chapter. By defining and characterizing the current state of the art in protein based markers, we are poised to evaluate and benchmark newly discovered protein biomarkers that will be isolated through new proteomics based investigations of urine.