Bladder Cancer refers to any of several types of malignant growths of the urinary bladder. It is a disease in which abnormal cells multiply without control in the bladder. The bladder is a hollow, muscular organ that stores urine; it is located in the pelvis. The most common type of bladder cancer begins in cells lining the inside of the bladder and is called urothelial cell or transitional cell carcinoma (UCC or TCC). Exposure to environmental carcinogens of various types is responsible for the development of most bladder cancers. Tobacco abuse (specifically cigarette smoking) is thought to cause 50% of bladder cancers discovered in male patients and 30% of those found in female patients. Thirty percent of bladder tumors probably result from occupational exposure in the workplace to carcinogens such as benzidine. Approximately 20% of bladder cancers occur in patients without predisposing risk factors. Bladder cancer is not currently believed to be heritable (i.e., does not "run in families" as a consequence of a specific genetic abnormality).

beta-hCG (beta human chorionic gonadotrophin)

• for T2-T4 bladder tumours, an elevated pre-treatment level of urinary beta-hCG is a marker of poor prognosis and may prove useful in deciding appropriate therapy. PMID: 8653319
• Measurement of serum and/or urine beta HCG appears to be an efficient diagnostic marker for the presence of distant metastases in bladder carcinoma. PMID: 2478247

Beta-2-microglobulin

• a differentiation marker in bladder cancer. PMID: 3534313

BLCA-1

• a urine based marker of bladder cancer which may be useful for the detection of this disease. PMID: 15947579

BLCA-4

• a bladder cancer specific biomarker, is present in urine samples from patients with bladder cancer, but not in samples from healthy individuals. PMID: 16360453
• a bladder cancer marker that is highly specific and occurs early in the development of the disease. PMID: 14977841
• Urinary BLCA-4 determination appears to have high potential as a test for screening and monitoring bladder cancer in the general population and in groups at high risk for the disease, such as those with spinal cord injury. PMID: 10953114

BTA (Bladder tumor antigen)

• in combination with urine cytology is a more useful way for diagnosing TCC of the bladder. PMID: 1891992

CA19-9 (Carbohydrate antigen 19-9)

• promising for use as a biomarker for the detection and monitoring of low-grade and low-stage bladder cancer, with the proviso that patients to be tested should be free of infection. PMID: 15764245

c-erbB-2

• the use of c-erbB-2 gene amplification, together with tumor grade and stage, could provide an accurate basis for determining the prognosis of bladder cancer. PMID: 10792078

Clusterin

• serum and urine clusterin can differ between bladder cancer patients and the control group. Urine clusterin could be the possible laboratory marker of bladder cancer. PMID: 16830064

CYFRA 21-1

• Patients with transitional cell cancer of the bladder with evidence of distant metastases showed a significant increase in serum CYFRA 21-1. During chemotherapy CYFRA 21-1 appears to be a potentially sensitive and useful indicator for monitoring treatment response. PMID: 16217281

Cytokeratin-18 (CK18)

• It is clear that serum cytokeratin-18 level increases in patients with bladder cancer. However, it can only be useful as a tumor marker in the diagnosis of T(3) and higher staged tumors. This study indicated that cytokeratin-18 does not have any diagnostic value in lower stage bladder cancers. PMID: 12135697

Cytokeratin-20 (CK20)

• a potential marker for bladder cancer, and is significantly more sensitive than urinary cytology. PMID: 9817302

DD23

• quantification in single cells may be particularly useful in targeting cystoscopic intervention for recurrence monitoring and, because of its high specificity, could be a tool for bladder cancer screening in high-risk groups. PMID: 8959319
• expression can be used as an adjunct to cytopathologic evaluation to enhance the sensitivity of urinary cytology detection of TCC. PMID: 12639642

EMA (Epithelial membrane antigen)

• could be a valuable indicator for histological grading or staging in pathological diagnosis and for predicting the survival of bladder cancer patients. PMID: 3303592

ERCC1

• a novel prognostic marker in advanced bladder cancer patients receiving cisplatin-based chemotherapy. PMID: 17229776

F-actin

• could be an early and sensitive marker for bladder cancer detection and risk prognostication. PMID: 2032215

FAS

• a promising novel urinary marker for the detection of recurrent superficial bladder cancer. PMID: 16541433

FBP (fucose-binding proteins)

• degree of expression of FBP binding sites correlates with the increased metastatic potential of bladder cancer and with poor patient survival times. PMID: 8339222

GNAS1

• a novel independent prognostic marker for clinical outcome supporting a functional role of G(alpha)s in bladder cancer progression. PMID: 15824158

H19

• can be used as a tumor marker in human bladder carcinoma, where its expression indicates a more malignant potential. PMID: 7855987
• Hyaluronic acid (HA), a glycosaminoglycan and known to promote tumor cell adhesion and migration, and its small fragments stimulate angiogenesis, is a new sensitive and specific urine marker for bladder cancer. PMID: 9044859

Hyaluronan (HA)

• HA in addition to being one of the best markers for the initial evaluation of bladder carcinoma can be used to determine the presence of a residual tumor. This is associated with poor prognosis. PMID: 16310928

Hyaluronidase

• a diagnostic urine marker for high-grade bladder cancer. PMID: 9044860

hTERT

• expression in urine sediments represents a reliable tool for the detection of primary urothelial neoplasms, equally specific, yet far more sensitive, than conventional cytology. PMID: 12893365

Lewis X antigen

• Lewis X antigen on exfoliated bladder cells enhances the detection of urothelial tumor cells, particularly from low grade and low stage neoplasms. PMID: 2405185

MMP-2 (matrix metalloproteinase-2)

• MMP-2 protein overexpression may be an independent prognostic biomarker for bladder cancer progression. PMID: 14624933

Neutral Endopeptidase

• will serve as a new tumor marker for bladder cancer as well as acute lymphatic leukemia. PMID: 7627835

NMP22 (Nuclear Matrix Protein 22)

• recurrence marker in bladder cancer. PMID: 10900760
• urinary NMP22 is a useful tool for the screening of urothelial cancer in patients with microscopic hematuria. PMID: 9170522, PMID: 9170521
• Urinary NMP22 is a useful diagnostic marker as a substitute for voided-urine cytology for the surveillance of urothelial cancer. PMID: 9076459

OCT-4

• an embryonic stem cell marker, is highly expressed in bladder cancer. PMID: 17205510

p53

• can be used as a tumor marker for bladder cancer. PMID: 15503000
• p53 nuclear immunostaining yields clinically relevant information and may be a useful tool for selecting patients with superficial bladder cancer who might be resistant to BCG. PMID: 15041112

Prothymosin-alpha

• urine prothymosin-alpha has the potential of being a useful tumor marker for the detection and follow-up of bladder cancer. PMID: 16461079

Survivin

• a sensitive marker for the noninvasive diagnosis of bladder cancer. PMID: 14713774

T antigen

• useful to predict the response of bladder tumors to treatment with bacillus Calmette-Guerin and interleukin-2. PMID: 2477561

Telomerase

• an important marker in the diagnosis of bladder cancer. PMID: 15153335
• the presence of telomerase in bladder washes may be a specific marker of bladder cancer, especially in low-grade tumors. PMID: 9533519
• can be determined in voided urine samples of patients with superficial bladder cancer. It has a higher sensitivity and specificity than conventional urinary cytology and is a good marker for diagnosis and follow-up of these patients. PMID: 10851728

Thymidine Kinase 1 (TK-1)

• a proliferation marker for determining prognosis and monitoring the surgical outcome of primary bladder carcinoma patients. PMID: 16391869

Thymidine Phosphorylase (TP)

• a prognostic marker for predicting recurrence in primary superficial bladder cancer. PMID: 16820903

TPA (Tissue polypeptide antigen)

• a useful marker not for the early detection of bladder cancer but for the monitoring of the efficacy of a treatment. PMID: 8694544

Transferrin Receptors (TFR)

• TFR activity in low grade superficial bladder tumours is a useful marker for predicting the recurrence rate. PMID: 2004229

UCA1 (urothelial carcinoma associated 1)

• a very sensitive and specific unique marker for bladder cancer. PMID: 16914571

Uroplakin II (UP II)

• might be a more useful marker than CK 20 for detecting micrometastases of bladder cancer in the pelvic lymph nodes, although a greater number of patients and longer followup are needed to come to a definitive conclusion. PMID: 16280744

XIAP

• a prognostic marker of early recurrence of nonmuscular invasive bladder cancer. PMID: 17439739

Other Bladder Cancer Markers

• Resting NOR had a predictive value in the prognosis of patients with invasive bladder tumor. PMID: 11564895
• Microvessel density (MVD) in bladder carcinoma correlates with grade, stage and malignant potential of the tumor. PMID: 15783115
• Hydronephrosis is a prognostic marker in bladder cancer in a cystectomy-only series. PMID: 16904815
• the Ce6-PVP formulation appeared to have the potential as a fluorescent marker for fluorescence diagnosis of human bladder cancer. PMID: 16516376
• noninvasive urinary glycosaminoglycan analysis may well provide a new biochemical approach for detecting and monitoring the pathogeneses of bladder cancer. PMID: 6793229