Multiprobe FISH for Enhanced Detection of Bladder Cancer in Voided Urine Specimens and Bladder Washings

Bubendorf, Lukas; Grilli, Bruno; Sauter, Guido; Mihatsch, Michael J.; Gasser, Thomas C.; Dalquen, Peter

doi:10.1309/k5p2-4y8b-7l5a-faa9

Cited by 210 publications

(163 citation statements)

References 19 publications

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“…9,25 Urovysiont FISH is one such molecular test that has been shown to have high sensitivity and specificity for the detection of urothelial carcinoma in urine. 8,14,19,21,26 We recently observed several cases of non-urothelial carcinoma that were Urovysiont FISH-positive. Others have also observed these coincidental overlaps with non-urothelial tumors.…”

Section: Discussionmentioning

confidence: 99%

“…17,18 Urovysiont FISH has a reported sensitivity of 73-92%, a specificity of 89-96% for urothelial carcinoma detection and several studies have confirmed its usefulness in the diagnosis and surveillance of these tumors. 8,14,[19][20][21][22] The test is designed to detect aneuploidy for chromosomes 3, 7, 17, and loss of the 9p21 locus in malignant urothelial cells that are shed in the urine of persons with urothelial carcinoma. These represent some of the most common chromosomal abnormalities in urothelial carcinoma.…”

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The use of Urovysion™ fluorescence in situ hybridization in the diagnosis and surveillance of non-urothelial carcinoma of the bladder

et al. 2009

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Urovysiont fluorescence in situ hybridization (FISH) is a sensitive and specific test used to diagnose urothelial carcinoma in urine. It detects aneuploidy of chromosomes 3, 7 and 17, and loss of both 9p21 loci in malignant urothelial cells. We evaluated Urovysiont FISH in non-urothelial carcinoma involving bladder to determine its possible application to their diagnosis and surveillance. Paraffin blocks from 31 non-urothelial bladder carcinomas, 12 pure urothelial carcinomas and 2 urothelial carcinomas with squamous differentiation were tested according to Vysis-Abbot Laboratories' recommended standards. Cases included 15 primary squamous carcinoma, 2 urothelial carcinoma with squamous differentiation, 4 primary adenocarcinoma, 5 colonic, 4 prostatic and 1 cervical adenocarcinoma. Total 60% of squamous, 83% of pure urothelial, 100% of urothelial carcinoma with squamous differentiation and 100% of primary and secondary adenocarcinomas hybridized successfully; 2/10 (11%) squamous carcinomas and 11/14 (79%) primary and secondary adenocarcinomas were Urovysiont FISH-positive with primary adenocarcinomas accounting for 75% (3/4), colonic, 80% (4/5), prostatic, 75% (3/4) and cervical, 100% (1/1) positivity. Total 70% (7/10) of pure urothelial carcinomas and 100% (2/2) of urothelial carcinomas with squamous differentiation were Urovysiont FISH-positive. In conclusion, we found that chromosomal abnormalities tested for by Urovysiont FISH may be seen in non-urothelial carcinomas of bladder. These false-positive results were frequent in primary and secondary adenocarcinoma and rare in squamous carcinoma. This has significant implications for the accurate diagnosis and management of patients with urinary tract cancer. Urovysiont FISH cannot be used to definitively diagnose squamous carcinoma or adenocarcinoma nor can it be used to differentiate the two from urothelial carcinoma. However, it may be useful as a surveillance tool in established primary and secondary bladder adenocarcinoma. Cytopathologists and urologists should correlate Urovysiont FISH results with cytomorphology and clinical information.

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Section: Discussionmentioning

confidence: 99%

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The use of Urovysion™ fluorescence in situ hybridization in the diagnosis and surveillance of non-urothelial carcinoma of the bladder

et al. 2009

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“…Such marker panel could be utilized for more specific molecular urine screening with microsatellite analyses 63 or interphase multicolor FISH. 64,65 The frequent chromosomal losses on 8p12-22 in many malignancies strongly suggest the presence of important tumor suppressor genes within this region. In bladder cancer, only three candidate genes have been investigated so far.…”

Section: Discussionmentioning

confidence: 99%

Deletions of chromosome 8p and loss of sFRP1 expression are progression markers of papillary bladder cancer

Stoehr

Wissmann²,

Suzuki³

et al. 2004

Laboratory Investigation

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Many molecular alterations are known to occur in urothelial carcinoma of the bladder, but their significance for tumor progression is poorly understood. Deletions of chromosome 8p are frequently found in several tumor types and are often associated with progressive disease. In all, 99 bladder tumors were screened for deletions at 8p using loss of heterozygosity (LOH) and multicolor fluorescence in situ hybridization FISH analyses. Allelic loss on chromosome 8p in at least one marker was found in 25/99 (25%) tumors. There was a significant correlation of 8p deletions with invasive tumor growth and a highly significant association with papillary growth pattern in patients with invasive disease. cDNA array analyses revealed that secreted Frizzled-related protein 1 (sFRP1), an antagonist of Frizzled receptors and Wnt pathway activation on chromosome 8p12-11.1, is frequently downregulated in bladder cancer. To investigate sFRP1 as a candidate for a putative progressionrelated gene on 8p, urothelial cell lines and primary urothelial carcinomas were screened for sFRP1 expression using quantitative real-time PCR, Northern blot, immunofluorescence and immunohistochemistry (IHC). Of the investigated bladder cancers, 38% showed loss of sFRP1 expression by quantitative RT-PCR. Evaluation of the protein expression by IHC using tissue microarrays containing 776 bladder cancers revealed loss or strong reduction of sFRP1 expression in 66% of cases. SFRP1 loss was associated with higher tumor stage and grade and shorter overall survival. In addition, loss of sFRP1 was an independent indicator of poor survival in patients with papillary but not with muscle invasive bladder cancer. There were neither mutations in the coding region of sFRP1 nor homozygous deletions at 8p12-11.21. However, promoter methylation was detected using methylation-specific PCR in 29% of cases. In conclusion, we could show a close correlation of chromosome 8p deletions and progression of papillary bladder tumors. The sFRP1 gene on chromosome 8p12-11.1 could be a candidate gene for the predicted, progression-related tumor suppressor gene in bladder cancer and could contribute to urothelial carcinogenesis.

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“…FISH is increasingly used by cytologists to identify neoplastic cells in various cytological specimens and has been shown to be more sensitive than conventional cytology for the detection of bladder cancer in urine specimens and biliary tract malignancy in endoscopic brushing specimens of the biliary tract. [12][13][14][15] FISH performed on esophageal brushing specimens may offer a more practical and accurate surveillance tool for patients with Barrett's esophagus because endoscopic brushing specimens can be obtained more rapidly than four-quadrant biopsies and can sample a larger percentage of the affected area. 13,16 Studies that used FISH to detect bladder cancer in urine specimens used a probe set that was tailored specifically for the detection of bladder cancer.…”

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The Development of a Fluorescence in Situ Hybridization Assay for the Detection of Dysplasia and Adenocarcinoma in Barrett's Esophagus

Brankley

Wang

Harwood

et al. 2006

The Journal of Molecular Diagnostics

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The goal of this study was to identify a set of fluorescence in situ hybridization probes for the detection of dysplasia and adenocarcinoma in patients with Barrett's esophagus. We examined 170 brushing specimens from 138 patients with Barrett's esophagus or a history of Barrett's esophagus using fluorescence in situ hybridization with probes to 5p15, 5q21-22, centromere 7, 7p12, 8q24.12-13, centromere 9, 9p21, centromere 17, 17p13.1, 17q11.2-12, 20q13.2, and centromere Y. Receiver-operator curves were used to determine the sensitivity and specificity of various four-probe combinations for detecting low-grade dysplasia, high-grade dysplasia, and esophageal adenocarcinoma. Endoscopic biopsy results were used as the gold standard. Numerous four-probe combinations provided a similarly high sensitivity and specificity. Of these, a set consisting of probes to 8q24, 9p21, 17q11.2, and 20q13.2 was found to have a sensitivity and specificity, respectively, of 70% and 89% for low-grade dysplasia, 84% and 93% for high-grade dysplasia, and 94% and 93% for esophageal adenocarcinoma. This probe set was chosen for future prospective clinical evaluations based on its high sensitivity and specificity, its ability to distinguish adenocarcinoma and high-grade or low-grade dysplasia from lesser diagnostic categories, and the favorable signal quality for each of the probes. The majority of esophageal adenocarcinomas is thought to arise in patients with Barrett's esophagus. Barrett's esophagus is a preneoplastic condition caused by metaplasia of the normal squamous mucosa of the distal esophagus into specialized intestinal mucosa containing goblet cells.1 Individuals with Barrett's esophagus have a 30-to 60-fold elevated risk of developing adenocarcinoma and develop adenocarcinoma at a rate of ϳ0.5 to 1.0% per year of follow-up. 2-5The American College of Gastroenterology has recommended that Barrett's esophagus patients be monitored for the development of dysplasia and adenocarcinoma by undergoing regular endoscopic examinations of the esophagus and obtaining four-quadrant biopsies for every 1 to 2 cm of affected esophagus.6,7 However, there are problems associated with the use of biopsies for monitoring Barrett's esophagus patients for the development of neoplasia including: 1) limited sampling of the affected mucosa leading to false-negative biopsy results, 8 2) lengthy procedure time required to take fourquadrant biopsies every 1 to 2 cm, 7 3) poor interobserver reproducibility of pathologists for the diagnosis of dysplasia, 9 and 4) relatively poor ability of histological findings to predict which patients are likely to progress to adenocarcinoma.10 Assays that improve the ability to accurately detect dysplasia and esophageal adenocarcinoma as well as predict which patients will progress to adenocarcinoma could markedly improve the clinical management of these patients. Conventional cytology is not routinely performed on endoscopic brushings obtained from patients with Barrett's esophagus in most institutions, and there are rel...

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Multiprobe FISH for Enhanced Detection of Bladder Cancer in Voided Urine Specimens and Bladder Washings

Cited by 210 publications

References 19 publications

The use of Urovysion™ fluorescence in situ hybridization in the diagnosis and surveillance of non-urothelial carcinoma of the bladder

The use of Urovysion™ fluorescence in situ hybridization in the diagnosis and surveillance of non-urothelial carcinoma of the bladder

Deletions of chromosome 8p and loss of sFRP1 expression are progression markers of papillary bladder cancer

The Development of a Fluorescence in Situ Hybridization Assay for the Detection of Dysplasia and Adenocarcinoma in Barrett's Esophagus

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