PMID- 15017433
OWN - NLM
STAT- MEDLINE
DCOM- 20041102
LR  - 20230210
IS  - 0893-3952 (Print)
IS  - 0893-3952 (Linking)
VI  - 17
IP  - 5
DP  - 2004 May
TI  - Chromosomal gains and genomic loss of p53 and p16 genes in Barrett's esophagus 
      detected by fluorescence in situ hybridization of cytology specimens.
PG  - 588-96
AB  - 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.
FAU - Fahmy, Mona
AU  - Fahmy M
AD  - Department of Anatomic and Clinical Pathology, The Cleveland Clinic Foundation, 
      Cleveland, OH 44195, USA.
FAU - Skacel, Marek
AU  - Skacel M
FAU - Gramlich, Terry L
AU  - Gramlich TL
FAU - Brainard, Jennifer A
AU  - Brainard JA
FAU - Rice, Thomas W
AU  - Rice TW
FAU - Goldblum, John R
AU  - Goldblum JR
FAU - Connor, Jason T
AU  - Connor JT
FAU - Casey, Graham
AU  - Casey G
FAU - Legator, Mona S
AU  - Legator MS
FAU - Tubbs, Raymond R
AU  - Tubbs RR
FAU - Falk, Gary W
AU  - Falk GW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Nucleic Acid Probes)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Barrett Esophagus/genetics/*pathology
MH  - Biopsy
MH  - *Chromosome Aberrations
MH  - Chromosomes, Human, Pair 11/genetics
MH  - Chromosomes, Human, Pair 12/genetics
MH  - Chromosomes, Human, Pair 17/genetics
MH  - Chromosomes, Human, Pair 6/genetics
MH  - Chromosomes, Human, Pair 7/genetics
MH  - Chromosomes, Human, Pair 9/genetics
MH  - Cyclin-Dependent Kinase Inhibitor p16/*genetics
MH  - Cytodiagnosis/methods
MH  - Esophagus/metabolism/pathology
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Nucleic Acid Probes/genetics
MH  - Sensitivity and Specificity
MH  - Tumor Suppressor Protein p53/*genetics
EDAT- 2004/03/16 05:00
MHDA- 2004/11/04 09:00
CRDT- 2004/03/16 05:00
PHST- 2004/03/16 05:00 [pubmed]
PHST- 2004/11/04 09:00 [medline]
PHST- 2004/03/16 05:00 [entrez]
AID - S0893-3952(22)04383-6 [pii]
AID - 10.1038/modpathol.3800088 [doi]
PST - ppublish
SO  - Mod Pathol. 2004 May;17(5):588-96. doi: 10.1038/modpathol.3800088.