Goal 1: To determine sensitivity and specificity of microsatellite analysis (MSA) of urine sediment, using a panel of 15 microsatellite markers, in detecting bladder cancer in participants requiring cystoscopy. This technique will be compared to the diagnostic standard of cystoscopy, as well as to urine cytology.
Goal 2: To determine the temporal performance characteristics of microsatellite analysis of urine sediment.
Goal 3: To determine which of the 15 individual markers or combination of markers that make up the MSA test are most predictive of the presence of bladder cancer.
Aim 1: This study will test the specificity of MSA in two groups of participants without bladder cancer─both healthy, normal controls as well as participants without bladder cancer who have conditions known to confound the performance of previous urinary tests for bladder cancer.
Aim 2: This study will test the sensitivity of MSA in the presence of clinically evident, pathologically confirmed bladder cancer.
Aim 3: This study will test the sensitivity and specificity of MSA for the detection of bladder cancer among participants undergoing surveillance for bladder cancer.
Aim 4: This study will test the value of MSA to predict subsequent development of bladder cancer among participants with a history of bladder cancer.
The “gold standard” in diagnosis and surveillance of bladder cancer is the macroscopic identification of disease during cystoscopy. Suspicious lesions are biopsied during cystoscopy, especially in participants with transitional cell carcinoma (TCC). The ideal test to replace cystoscopy or decrease the frequency of the surveillance cystoscopy in the management of bladder cancer would be technologically driven, highly sensitive, and rapid.
Microsatellites are tandem repeat DNA sequences that are common, highly polymorphic genetic elements within the eukaryotic genome. Alterations, either expansion or deletions, of microsatellites were used as clonal markers for the detection of human cancer, including bladder cancer (Mao, Lee, Tockman, Erozan, Askin, & Sidransky, 1994).16 In preliminary studies, Mao et al., (1996)7 and Mourah et al., (1998)10 showed that microsatellite markers had high sensitivity and specificity in detecting bladder cancer in the voided urine specimens (Mao, Schoenberg, Scicchitano et al., 1996;7 Mourah, Cussenot, Vimont, et al., 1998).10 Further development of microsatellite testing to improve specificity, speed of testing, and operator efficiency may improve bladder cancer management.
The microsatellite analysis described herein is based on Short Tandem Repeats (STR). The assay has been derived employing the STR technology. The STR allele designations and peak heights from the participant control sample (blood) are compared to the allele designations and peak heights from the participant urine sample. The purpose of the analysis is to identify loss of heterozygosity (LOH) and instability present in the urine sample.
The National Cancer Institute's Division of Cancer Prevention has released a new funding opportunity to solicit organ-specific applications for Biomarker Developmental Laboratories (BDLs), one of the four scientific units of the recently funded Early Detection Research Network (EDRN). The EDRN is a national infrastructure funded to discover, develop, and validate biomarkers for risk assessment, detection, and molecular diagnosis and prognosis of early cancer. BDLs are responsible for the discovery, development, characterization, and testing of new, or the refinement of existing, biomarkers and biomarker assays for risk assessment, detection, and molecular diagnosis and prognosis of cancers.
The existing BDLs are primarily focused on ovary and gastrointestinal cancers. The proposed BDLs (to be supported under this funding opportunity) should be focused on one or more of the following cancers: breast, prostate and other genitourinary organs, or lung. In addition, cancers with rapidly rising incidence rates, e.g., endometrial, hepatocellular, kidney, thyroid, oropharyngeal cancers, and/or cancers with unique etiology, e.g., mesothelioma, will be considered.
The newly funded units of the Early Detection Research Network will be announced later in April. Successful applicants have already been notified. Those researchers who were not successful during the last round of applications are encouraged to apply to this opportunity.