Comparison of the ImmunoCyt test and urinary cytology with other urine tests in the detection and surveillance of bladder cancer

Abstract

Despite several new urine markers urinary cytology remains the gold standard for the non-invasive detection of bladder carcinoma. The use of monoclonal antibodies against tumor associated antigens offers a promising approach to improve urinary cytology. The aim of this study was to compare fluorescence immunocytology (ImmunoCyt/Ucyt+ test), alone and in combination with the conventional cytology, with other urine markers. Urine samples from 126 patients undergoing cystoscopy were included in the study. Among them, 42 patients had urothelial carcinoma, two dysplasia, two other malignancies, and 78 had no evidence of bladder cancer. Urine samples were taken before any manipulation. We used the ImmunoCyt test and Papanicolaou staining for conventional cytology. The ImmunoCyt slides were examined under a fluorescence microscope. Evaluations of the tests were blinded to clinical and pathological data and were carried out by three independent observers. The results of cytology and ImmunoCyt were compared with the BTAstat, NMP22, Lewis X, 486p3/12, and Urovision tests. The sensitivity for the ImmunoCyt test was 78.3% and for conventional cytology 84.6%. The combination of ImmunoCyt and cytology showed a sensitivity of 89.1%. The specificity was 73.8% for the ImmunoCyt alone, 80.0% for the cytology, and 72.5% for the combination of ImmunoCyt and cytology. Sensitivities for the other tests were 68.8% for (FISH), 66.6% (BTA-Stat), 68.8% (486p3/12), 95.5% (Lewis X), and 71.1% for (NMP22). Specificity was 89.1% for (FISH), 78.2% (BTA-Stat), 76.4% (486p3/12), 32.8% (Lewis X), and 65.5% for (NMP22). Urinary cytology can be improved by immunostaining with monoclonal antibodies against tumor-associated antibodies. The combination of ImmunoCyt with conventional cytology offers a superior sensitivity to other commercial tests. The ImmunoCyt test provides a useful supplement to urinary cytology in the diagnosis of bladder cancer.

Biomarkers for detection and surveillance of bladder cancer

“…Specificity of the Bladder Cancer Test is reported to be 60.0%-95.0%, and specificity of the NMP22 BladderChek is reportedly in the range of 40.0%-89.8%. 11,[19][20][21][22][23]25,26,32,34,36,37,[39][40][41][42] The NMP22 tests are based on the release of NMPs into the urine following apoptosis of the urothelial cells, a process that can also occur as a result of benign conditions. As is the case with the BTA tests, NMP22 levels are raised in patients with urinary tract infections, concurrent urolithiasis, history of bladder interposition, other malignancies, intravesical therapies and even cystoscopy, all of which may contribute to false-positive results.…”

“…Specificity of the combined assay reaches 61.0%-77.7%, which is less than that offered by cytology alone. 27,[31][32][33]38,39 The ImmunoCyt/uCyt+ assay requires technical expertise, extensive sample handling and preparation and specialized equipment. However, a person with minimal cytology training and experience can perform the test.…”

“…The loss of the 9p21 locus, site of the p16 tumour suppressor gene, is the earliest and most frequent genetic aberration in bladder cancer. 62 Recent published series on the FISH assay have demonstrated results in the range of 68.6%-100% and 65.0%-96.0% for sensitivity and specificity, respectively 18,28,30,35,39,43,44,58,62,63 (Table 1). Thus the UroVysion assay, which has received FDA approval for the detection of recurrent bladder cancer, is more sensitive than urinary cytology but provides a similar, or slightly lower, specificity.…”

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Liver, Bladder, Cervical, and Gastric Cancers

“…According to one recent report, the test has a sensitivity of 81% and specificity of 75% in detecting bladder cancer (258 ). The ImmunoCyt test was evaluated in several earlier investigations (259,260 ) with similar findings (259,260 ). When used with cytology, the ImmunoCyt test appears to improve the detection of low-grade tumors (261 ).…”

Serum Periplakin as a Potential Biomarker for Urothelial Carcinoma of the Urinary Bladder

“…Use of urine cytology is limited because of its low sensitivity. For these reasons, some tumor markers have been investigated (eg, BTAstat, NMP22), but their sensitivity and specificity are limited and not superior to urine cytology (Toma et al, 2004). To overcome these limitations, preoperative molecular markers are expected to be used as a minimally invasive method for assisting in and predicting a precise diagnosis in patients with UCB (Ghafouri-Fard et al, 2014).…”