Table 2: Current and emerging urinary biomarkers.

Urine biomarkerCurrent status of developmentReference

Bladder tumor antigen (BTA)Bladder tumor-associated antigen in urine can be detected. The human complement factor H-related protein (hCFHrp) can be detected in the urine. Quantitative (BTA-TRAK) and qualitative (BTA-stat) assays have been done. Accepted for being used with cystoscopy. Sensitivity 50–90%; specificity 90%; false positive in urinary tract infections, calculi, benign prostatic hyperplasia and with intravesical BCG or chemotherapy (specificity 50%).[911]

Genetic aberrations(i) FISH: detection of genetic alterations in exfoliated cells in the urine (aneuploidy of chromosomes 3, 7, 17; loss of 9p21). Cystoscopy is able to detect those patients that are going to have an early relapse after all the treatment.
(ii) Loss of heterozygosity and microsatellite alterations in multiple chromosomes can be detected by PCR.

Nuclear matrix proteins
 (i) NMP22
 (ii) NMP52
 (iii) BCLA4
 (iv) BCLA1
Multiple nuclear matrix proteins are overexpressed in urothelial tumors and, after the apoptosis of these cells, released into the urine. The most studied one is NMP22, whose sensitivity is higher in high grade and in nonmuscle invasive tumors. Its levels are associated with disease recurrence and progression and it can be used together with the cystoscopy.[1619]

 (i) CK8
 (ii) CK18
 (iii) CK19
 (iv) CK20
Cytokeratins (CKs) are proteins from the epithelial cellular cytoskeleton. Different types of CK can be over-expressed in different epithelium, so we can find specific CKs in urine in bladder cancer patients. They can be detected by ELISA or by RT-PCR. Their usefulness is under additional studies.[15, 20, 21]

Hyaluronic acid (HA) and
hyaluronidase (HAase)
Both are measured by ELISA-like assays. HA regulates cell adhesion, so it can promote tumor progression and distant metastases. HAase cuts HA into small pieces promoting angiogenesis. These markers have promising results, thus having apparent ability to detect low grade tumors better than other urine biomarkers.[22, 23]

SurvivinAn inhibitor of apoptosis that can be detected in urine by RT-PCR techniques. New studies are needed.[24]

OthersFibrin degradation products, DD23, Lewis X antigen.[2527]