Bladder cancer markers

A fluorescence in situ hybridization (FISH) technique, UroVysion, uses fluorescently labeled probes to detect aneu-ploidy of chromosomes 3,7, and 17, and deletion of the 9p21 locus that contains the tumor suppressor pi6, which is the most common alteration seen in urothelial carcinoma. Table 23-13 compares cytology with that of UroVysion for the detection of bladder cancer. 

Nuclear matrix proteins (NMPs) make up the internal structure of the nucleus. Their function has been associated with regulating key reactions in the nucleus, such as DNA reph-cation and RNA synthesis. The NMPs released by the cancer cell may be different from the normal cell. Furthermore, different types of cells may have different NMPs. Soluble NMPs could be detected in the sera of cancer patients in higher concentrations than the sera from normal subjects. In a multicenter foUow-up study (125 cystoscopies) of 90 patients with 33 pathologically confirmed TCC of the urinary tract, 70% of the 33 recurrences had urinary NMP greater than lOU/mL. Of the patients with NMP less than lOU/mL, 86% had no malignancy at subsequent cystoscopy.  

An ELISA for the measurement of an NMP called nuclear mitotic apparatus protein in urine sample has been approved by the U.S. FDA for the management of patients with TCC of the urinary tract. The test is called NMP22 and is manufactured by Matritech, Inc. (Newton, Mass.) 

A qualitative test for BTA analytes in urine, termed the BTA stat. test, has been developed. BTA analytes are high molecular weight polypeptides composed of complexes of basement membrane proteins. The presence of BTA analytes in urine is thought to involve either invasion of the basement membrane by tumor, production by the tumor itself, or a combination of these, which maybe linked with the bodjfs immune response. If BTA analytes are present in a significant level, they will combine with latex particles to produce an agglutination reaction, which produces a visible color change on the 

From Sarosdy, M.E, Schellhammer, R, Bokinsky, G et al. Clinical evaluation of a multi-target fluorescent in situ hybridization assay for detection of bladder cancer. / Uwl 2002 168 1950-4. 

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The utility of protein expression mapping using 2D gel electrophoresis and mass spectrometry has been demonstrated for several experimental systems. One application has been to assess the differences in protein expression between normal and cancerous cells. For example, expression mapping has been used to identify protein markers for bladder cancer (Ostergaard et al., 1999). This was accomplished by identifying proteins released into the urine of patients with and without bladder cancer using 2D electrophoresis and mass spectrometry. 

Intravesical infusion of linear PEI/pDNA polyplexes was evaluated in patients with superficial bladder cancer where intravesical therapy with bacillus Calmette-Guerin had failed [6, 224]. Patients had low grade superficial bladder cancer, which expressed H19. The therapeutic pDNA contains H19 gene regulatory sequences that drive the expression of an intracellular toxin. Escalating doses of 2-20 mg plasmid per intravesical treatment were applied, with responders continuing to receive polyplexes once a month every month for 1 year. The treatment resulted in complete ablation of the marker tumor, without any new tumors in four of the 18 patients (22% overall complete response rate). Eight of the 18 patients (44%) had complete marker tumor ablation or a 50% reduction of the marker lesion. 

Sidi AA, Ohana P, Benjamin S, Shalev M, Ransom JH, Lamm D, Hochberg A, Leibovitch I (2008) Phase I/II marker lesion study of intravesical BC-819 DNA plasmid in H19 over expressing superficial bladder cancer refractory to bacillus Calmette-Guerin. J Urol 180 2379-2383... 

Hung RJ, Brennan P, Malaveille C et al. Using hierarchical modeling in genetic association studies with multiple markers application to a case-control study of bladder cancer. Cancer Epidemiol Biomarkers Prev 2004 13 1013—1021. 

Moreover, Cellis et al. have been working on identifying protein markers that may be valuable for diagnosis and follow-up of bladder cancer patients. To achieve this goal, they have focused on the establishment of a comprehensive 2D gel database of urine proteins. 

Lokeshwar, V.B. et al., Tumor-associated hyaluronic acid a new sensitive and specific urine marker for bladder cancer, Cancer Res., 57, 773, 1997. 

Diagnostic potential in bladder cancer of a panel of tumor markers (calreticulin, gamma-synuclein, and catechol-o-methyltransferase) identified by proteomic analysis. Cancer Sci. 95, 955-961. 

Kageyama S, Isono T, Iwaki H, Wakabayashi Y, Okada Y, et al. Identification by proteomic analysis of cal-reticulin as a marker for bladder cancer and evaluation of the diagnostic accuracy of its detection in urine. Clin Chem 2004 50 857-66. 

A series of recent studies have pointed to the potential prognostic value of receptor tyrosine kinase (RTK) markers such as FGFR-3, EGFR, and other ERB family members (ERBB2/F1ER2 and ERBB3) in superficial and invasive bladder cancer disease (Table 16.9). 

Brunner A, Verdorfer I, Prelog M, et al. Large-scale analysis of cell cycle regulators in urothelial bladder cancer identifies pi 6 and p27 as potentially useful prognostic markers. Pathobiology. 2008 75 25. 

McShane LM, Aamodt R, Cordon-Cardo C, et al. Reproducibility of p53 immunohistochemistry in bladder tumors. National Cancer Institute, Bladder Tumor Marker Network. Clin Cancer Rcs.2000 6 1854. 

Clairotte A, Lascombe I, Fauconnet S, et al. Expression of E-cadherin and alpha-, beta-, gamma-catenins in patients with bladder cancer identification of gamma-catenin as a new prognostic marker of neoplastic progression in T1 superficial urothelial tumors. Am J Clin Pathol. 2006 125 119. 

Detection of epidermal growth factor receptor mRNA in peripheral blood a new marker of circulating neoplastic cells in bladder cancer patients. Clin Cancer Res, 7, 577-583. 

Ostergaard M et al. Proteome profiling of bladder squamous cell carcinomas identification of markers that define their degree of differentiation. Cancer Res 1997 57 4111 117. 

The aberrant expression of MARBPs upon malignant transformation makes them a reliable marker for diagnosis of advanced diseased conditions. For instance, the NMP 22 levels in urine have now been routinely used to identify bladder and ductal cancer. Similarly, pi 14 MAR-binding activity has been detected in aggressive mmors, while significantly weaker pi 14 activity has been observed in... 

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