A Comparison of Cytology and Fluorescence in Situ Hybridization for the Detection of Urothelial Carcinoma

Halling, Kevin C.; King, Walter; Соколова, И. А.; Meyer, Reid G.; Burkhardt, Haleh M.; Halling, Amy C.; Cheville, John C.; Sebo, Thomas J.; Ramakumar, Sanjay; Stewart, Christopher S.; Pankratz, Shane; O’Kane, Dennis J.; Seelig, Steven; Lieber, Michael M.; Jenkins, Robert B.

doi:10.1016/s0022-5347(05)67104-2

Cited by 341 publications

(171 citation statements)

References 41 publications

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“…22 Only sparse data are available in the literature regarding the use of FISH on endoscopic brush cytology specimens for biomarker assessment in Barrett's esophagus. Recently, a group of investigators from Denmark applied FISH to cell pellets obtained from endoscopic brushings, and analyzed the aneusomic states of chromosomes 4,8,20, and Y, as well as genomic losses of p16, p53, and retinoblastoma (Rb) gene loci. 44 This study showed that while aneusomy of chromosomes 4 and 8, and a p16 locus deletion are early changes present in the metaplastic Barrett's epithelium, p53 genomic loss (and rarely Rb loss) occurs predominantly in HGD and adenocarcinoma arising in Barrett's esophagus.…”

Section: Discussionmentioning

confidence: 99%

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Chromosomal gains and genomic loss of p53 and p16 genes in Barrett's esophagus detected by fluorescence in situ hybridization of cytology specimens

et al. 2004

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Endoscopic brush cytology is a promising surveillance technique for Barrett's esophagus. Ancillary markers are sought to increase the sensitivity of cytology and allow identification of patients at increased risk for disease progression. To determine if there are specific genetic changes in Barrett's esophagus with associated high-grade dysplasia/intramucosal adenocarcinoma compared to those without dysplasia, we performed fluorescence in situ hybridization (FISH) on cytologic specimens using probes to chromosomes and genomic regions previously described as altered in this disease. We studied archival brush cytology slides from 40 Barrett's esophagus patients: 21 with biopsy-proven high-grade dysplasia/carcinoma and 19 with no dysplasia and a minimum 5 years of negative follow-up. Centromeric enumeration probes (CEP) for chromosomes 6, 7, 11, and 12, and locus-specific probes (LSI) for 9p21 (p16 gene), and 17p13.1 (p53 gene) loci along with their corresponding CEP (9 and 17, respectively) were used in this study. A positive FISH result was defined as the presence of cells with 42 CEP signals or with a loss of the LSI signals relative to their corresponding CEP. p53 locus loss and/or aneusomy of chromosomes 6, 7, 11, and 12 abnormalities could be detected by FISH in routinely processed endoscopic brush cytology specimens from 95% of biopsy-positive cases with a specificity of 100%. Interestingly, all five cases with cytologic changes classified as indefinite for dysplasia from patients with a positive biopsy showed changes by FISH. Loss of the p16 locus was seen commonly in patients both with and without dysplasia/carcinoma. Selected biomarkers from this study merit further investigation to determine their potential to detect genetic changes in patients with Barrett's esophagus prior to the development of high-grade dysplasia.

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Section: Discussionmentioning

confidence: 99%

“…Furthermore, abnormalities detectable by FISH may precede the evidence of carcinoma on bladder biopsies. 8,9 FISH has also shown promise in the detection of carcinomas of the breast, lung, and colon. [10][11][12][13] Multiple genetic abnormalities have been reported in Barrett's esophagus-associated adenocarcinoma and its precursors.…”

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Chromosomal gains and genomic loss of p53 and p16 genes in Barrett's esophagus detected by fluorescence in situ hybridization of cytology specimens

et al. 2004

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“…7 The gold standard for diagnosis and surveillance of urothelial carcinoma has traditionally been cystoscopy and urine cytology, however both have limitations. [8][9][10][11][12][13][14] Although urine cytology is excellent for detecting high-grade urothelial carcinoma (sensitivity and specificity 475%), it has a low sensitivity (20-60%) for detecting low-grade tumors. 8,[10][11][12][13][14] The low sensitivity of urine cytology, the invasiveness of cystoscopy and its limited usefulness in detecting flat and inaccessible lesions have prompted increased demand for newer, more sensitive and non-invasive tests for detection of urothelial carcinoma.…”

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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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“…Fluorescence in-situ hybridisation (FISH) of exfoliated bladder cells has been shown to have a greater sensitivity than conventional urine cytology in the detection of transitional cell carcinoma of the bladder (Halling et al, 2000). Possibly therefore, detection of early chromosomal changes indicative of genomic instability at the enterovesical anastomosis in patients who have undergone enterocystoplasty may identify those at high risk of tumorigenesis before a potentially fatal cancer has occurred.…”

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Fluorescence in-situ hybridisation on biopsies from clam ileocystoplasties and on a clam cancer

et al. 2006

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The incidence of carcinoma following an enterocystoplasty increases with time and is a major concern after such procedures. The aim of this study was to investigate genetic instability (in the form of numerical chromosomal aberrations) at the enterovesical anastomosis in patients who had undergone a clam ileocystoplasty using fluorescent in-situ hybridisation (FISH). Fluorescent in-situ hybridisation was performed on touch preparation samples prepared from fresh endoscopic biopsies obtained from the enterovesical anastomosis and native bladder remnant (control specimens) of 15 patients who had undergone a clam ileocystoplasty. Fluorescent in-situ hybridisation was also performed on one squamous cell cancer specimen. Significant aneusomic changes were found at the enterovesical anastomosis in all 15 patients. Alterations in chromosome 18 copy number were the most frequent abnormal finding (trisomy 18, n ¼ 8; monosomy 18, n ¼ 7). Nine patients were monosomic for chromosome 9. Isolated monosomy 8 and trisomy 8 were each found in one patient. The control specimens were all normal. An unusually high incidence of polysomic cells was found in the clam tumour specimen, reflecting the aggressive nature of this cancer. Chromosomal numerical abnormalities occur at the enterovesical anastomosis following a clam ileocystoplasty and chromosome 18 appears to be a particularly good marker of genetic instability. The results of this study indicate that morphologically normal tissue obtained from the enterovesical anastomosis displays evidence of chromosomal instability that may predispose to tumour formation. However, further prospective, blinded, longitudinal studies are required to establish whether predetermined FISH signal patterns in enterocystoplasty cells in urine or obtained by biopsy predict the presence or absence of tumour.

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A Comparison of Cytology and Fluorescence in Situ Hybridization for the Detection of Urothelial Carcinoma

Cited by 341 publications

References 41 publications

Chromosomal gains and genomic loss of p53 and p16 genes in Barrett's esophagus detected by fluorescence in situ hybridization of cytology specimens

Chromosomal gains and genomic loss of p53 and p16 genes in Barrett's esophagus detected by fluorescence in situ hybridization of cytology specimens

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

Fluorescence in-situ hybridisation on biopsies from clam ileocystoplasties and on a clam cancer

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