Chromosomal gains and genomic loss of p53 and p16 genes in Barrett's esophagus detected by fluorescence in situ hybridization of cytology specimens
| Autor: | Marek Skacel, Gary W. Falk, Jennifer Brainard, Graham Casey, Raymond R. Tubbs, Mona S Legator, Jason T. Connor, John R. Goldblum, Thomas W. Rice, Mona Fahmy, Terry Gramlich |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Pathology
medicine.medical_specialty Biopsy Cytodiagnosis Locus (genetics) Biology Sensitivity and Specificity Pathology and Forensic Medicine Barrett Esophagus Esophagus Cytology medicine Carcinoma Humans Cyclin-Dependent Kinase Inhibitor p16 In Situ Hybridization Fluorescence Chromosome Aberrations Chromosomes Human Pair 12 medicine.diagnostic_test Chromosomes Human Pair 11 medicine.disease Nucleic Acid Probes medicine.anatomical_structure Dysplasia Barrett's esophagus Chromosomes Human Pair 6 Tumor Suppressor Protein p53 Chromosomes Human Pair 9 Chromosomes Human Pair 7 Fluorescence in situ hybridization Chromosomes Human Pair 17 |
| Zdroj: | Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 17(5) |
| ISSN: | 0893-3952 |
| Popis: | 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 >2 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. |
| Databáze: | OpenAIRE |
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