Markers of bladder cancer diagnosis and prognosis will be developed and evaluated as part of the NCI Bladder Tumor Marker Network. Candidate markers will be selected based on clinical significant in a phased approach, starting with small pilot studies at UCSF to define assay conditions, test prevalence, and determine clinical significant Studies will then be proposed for the full Network using material from Member tissue banks. Markers will be considered for clinical application based on their biology, and will be tested for clinical significance in a defined context. Areas of need for prognostic markers include: prediction of recurrence or progression in superficial disease; prediction of metastasis in invasive cancer; and prediction of response to therapy. Network studies will have highest priority. Specimen acquisition of prospective and retrospective material will occur at UCSF Moffitt, Mt. Zion and SFVA medical centers. UCSF has been responsible for Network analyses of Proliferation (Ki67), angiogenesis, and molecular cytogenetics (FISH). These activities will continue, with additional responsibility for coordinating correlative superficial tumor marker studies in collaboration with the South West Oncology Group (SWOG). UCSF will also continue to coordinate quality control studies to define sources of variation in interlaboratory comparisons of molecular cytogenetics and proliferative immunohistochemistry assays. Molecular cytogenetic assays will be the focus of marker developments. Fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) will be used to define markers of tumor progression l) Abnormalities in the bladder field will be examined by centromeric FISH analysis of exfoliated cells and of grossly normal appearing biopsies from patients with concurrent tumors. 2) CGH will be used to define clonal relationships between multiple or recurrent tumors to distinguish tumor spread vs. a field defect as their cause. 3) Section FISH and CGH will be used to identify early genetic changes in premalignant disease (CIS and dysplasia) 4) CGH will be used to identify chromosomal alterations which are more fluent in tumor metastases than primaries in paired samples. 5) CGH will be used to link overall levels of DNA gains and losses (genetic instability) with clinical outcome in invasive tumors. 6) Amplification of chromosome 20q will be detected by FISH to evaluate the potential significance of this newly defined genetic abnormality.
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