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Improved detection of bladder carcinoma cells in voided urine by standardized microsatellite analysis


Frigerio, Simona; Padberg, Barbara C; Strebel, Räto T; Lenggenhager, Daniela; Messthaler, Angelika; Abdou, Marie-Therese; Moch, Holger; Zimmermann, Dieter R (2007). Improved detection of bladder carcinoma cells in voided urine by standardized microsatellite analysis. International Journal of Cancer, 121(2):329-338.

Abstract

Successful treatment of bladder cancer depends largely on early diagnosis of primary and recurrent disease. Sensitive, specific and noninvasive procedures for detection are especially needed for grade 1 and 2 bladder tumors, because of the relatively low sensitivity of cytology. Here we introduce a novel strategy to improve the sensitivity and reliability of microsatellite analyses by employing marker-specific threshold values for loss-of-heterozygosity (LOH) at 10 loci. These individual cut-offs were experimentally determined with 35 normal control tissues and subsequently validated in a retrospective study with bladder cancer biopsies from 86 patients. In a prospective analysis of voided urines samples and matched blood probes from 91 patients, LOH-analysis, UroVysion FISH and conventional urine cytology were compared with histological findings of consecutive transurethral biopsies. Whereas all samples could be analyzed by our LOH assay, only 56 samples were suitable for all 3 analyses. The highest sensitivity was obtained with our LOH-assay/cytology approach (G1-2: 72%; G3: 96%) being only surpassed by a combination of all 3 techniques (G1-2: 83%; G3: 100%). Since over 93% of the patients with recurrent disease were identified by LOH/cytology-analyses of their voided urine samples, a monitoring scheme alternating cystoscopy with LOH/cytology-examination could now be envisioned to reduce invasive interventions and consequently improve follow-up compliance, especially in patients with low grade tumors.

Abstract

Successful treatment of bladder cancer depends largely on early diagnosis of primary and recurrent disease. Sensitive, specific and noninvasive procedures for detection are especially needed for grade 1 and 2 bladder tumors, because of the relatively low sensitivity of cytology. Here we introduce a novel strategy to improve the sensitivity and reliability of microsatellite analyses by employing marker-specific threshold values for loss-of-heterozygosity (LOH) at 10 loci. These individual cut-offs were experimentally determined with 35 normal control tissues and subsequently validated in a retrospective study with bladder cancer biopsies from 86 patients. In a prospective analysis of voided urines samples and matched blood probes from 91 patients, LOH-analysis, UroVysion FISH and conventional urine cytology were compared with histological findings of consecutive transurethral biopsies. Whereas all samples could be analyzed by our LOH assay, only 56 samples were suitable for all 3 analyses. The highest sensitivity was obtained with our LOH-assay/cytology approach (G1-2: 72%; G3: 96%) being only surpassed by a combination of all 3 techniques (G1-2: 83%; G3: 100%). Since over 93% of the patients with recurrent disease were identified by LOH/cytology-analyses of their voided urine samples, a monitoring scheme alternating cystoscopy with LOH/cytology-examination could now be envisioned to reduce invasive interventions and consequently improve follow-up compliance, especially in patients with low grade tumors.

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29 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:15 July 2007
Deposited On:08 Jul 2015 10:09
Last Modified:08 Dec 2017 13:21
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:0020-7136
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1002/ijc.22690
PubMed ID:17373664

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