Type of test Urine

Normal findings

 BTA: < 14 units/mL

NMP22: < 10 units/mL

FISH: No chromosomal amplification or deletions noted

 Test explanation and related physiology

 The recurrence rate for superficial bladder cancers that have been resected by transurethral cystoscopy is high. Surveillance testing requires frequent urine testing for cytology and frequent cystoscopic evaluations. The use of bladder tumor markers may provide an easier, cheaper, and more accurate method of diagnosing recurrent bladder cancer.

Bladder tumor antigen (BTA) and nuclear matrix protein 22 (NMP22) are proteins produced by bladder tumor cells and deposited into the urine. Normally none or very low levels of these proteins are found in the urine. When levels of bladder cancer tumor markers are normal, cystoscopy rarely yields positive results. When these markers are elevated, bladder tumor recur rence is strongly suspected and cystoscopy is indicated to confirm bladder cancer recurrence.

NMP22 may also be a good screening test for patients at increased risk for developing bladder cancer. However, these markers can be elevated in other circumstances (i.e., recent urologic surgery, urinary tract infection, calculi). Cancers involving the ureters and renal pelvis may also be associated with increased BTA and NMP22.

Bladder cancer cells have been found to exhibit aneuploidy (gene amplifications on chromosomes 3, 7, and 17, and the loss of the 9p21 locus on chromosome 9). Using DNA probes, through fluorescence in situ hybridization (FISH), these chromosomal abnormalities can be identified with great accuracy. FISH can be performed on cells isolated in a fresh urine specimen or cells available on a ThinPrep slide (similar to Pap smears .

Although not a tumor marker, a cytology test is available that can be used in the early detection of bladder cancer recurrence. It is an immunocytofluorescence technique based on monoclonal antibodies to two antigens: a mucin glycoprotein and a carcinoembryonic antigen (CEA). These antigens are expressed by tumor cells found in patients with bladder cancer and are exfoliated in the urine.

Interfering factors

• These proteins are very unstable. If the urine is not immediately stabilized, false negatives may occur.

 • Active infection (including sexually transmitted diseases) of the lower urologic tract can cause false elevations.

 • Kidney or bladder calculi can cause false elevations.

Procedure and patient care

 • See inside front cover for Routine Urine Testing.

* Tell the patient that no fasting is required.

 • A urine specimen should be collected, preferably from the first void of the day.

• The specimen should be transported to the laboratory immediately to avoid deterioration of the cells.

• If a time delay is required, the specimen should be refrigerated.

Abnormal findings

- Bladder cancer

- Nonbladder urologic cancer (e.g., ureters, renal pelvis)