Fluorescence in situ hybridization identifies high risk Barrett's patients likely to develop esophageal adenocarcinoma

S. M. Brankley, K. C. Halling, S. M. Jenkins, M. R. Timmer, Prasad G Iyer, Thomas Christopher Smyrk, E. G. Barr Fritcher, J. S. Voss, B. R. Kipp, M. B. Campion, L. S. Lutzke, D. M. Minot, Kenneth Ke Ning Wang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Barrett's esophagus (BE) with high-grade dysplasia (HGD) defines a group of individuals at high risk of progression to esophageal adenocarcinoma (EA). Fluorescence in situ hybridization (FISH) has been shown to be useful for the detection of dysplasia and EA in endoscopic brushing specimens from BE patients. The aim of this study was to determine whether FISH in combination with histological findings would further identify more rapid progressors to EA. This is a retrospective cohort study of high-risk patients, having a history of biopsy-confirmed HGD without EA, with an endoscopic brushing specimen analyzed by FISH while undergoing endoscopic surveillance and treatment between April 2003 and October 2010. Brushing specimens were assessed by FISH probes targeting 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2), and 20q13 (ZNF217) and evaluated for the presence of polysomy, defined as multiple chromosomal gains (displaying ≥ 3 signals for ≥ 2 probes). Specimens containing ≥ 4 cells exhibiting polysomy were considered polysomic. HGD was confirmed by at least two experienced gastrointestinal pathologists. Of 245 patients in this study, 93 (38.0%) had a polysomic FISH result and 152 (62.0%) had a non-polysomic FISH result. Median follow-up was 3.6 years (interquartile range [IQR] 2-5 years). Patients with a polysomic FISH result had a significantly higher risk of developing EA within 2 years (14.2%) compared with patients with a non-polysomic FISH result (1.4%, P < 0.001). These findings suggest that a polysomic FISH result in BE patients with simultaneous HGD identifies patients at a higher risk for developing EA compared with those with non-polysomy.

Original languageEnglish (US)
JournalDiseases of the Esophagus
DOIs
StateAccepted/In press - 2015

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Fluorescence In Situ Hybridization
Adenocarcinoma
Barrett Esophagus
Cohort Studies
Retrospective Studies
Biopsy

Keywords

  • Barrett's esophagus
  • Cytology
  • Esophageal adenocarcinoma
  • FISH
  • Polysomy

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Fluorescence in situ hybridization identifies high risk Barrett's patients likely to develop esophageal adenocarcinoma. / Brankley, S. M.; Halling, K. C.; Jenkins, S. M.; Timmer, M. R.; Iyer, Prasad G; Smyrk, Thomas Christopher; Barr Fritcher, E. G.; Voss, J. S.; Kipp, B. R.; Campion, M. B.; Lutzke, L. S.; Minot, D. M.; Wang, Kenneth Ke Ning.

In: Diseases of the Esophagus, 2015.

Research output: Contribution to journalArticle

Brankley, SM, Halling, KC, Jenkins, SM, Timmer, MR, Iyer, PG, Smyrk, TC, Barr Fritcher, EG, Voss, JS, Kipp, BR, Campion, MB, Lutzke, LS, Minot, DM & Wang, KKN 2015, 'Fluorescence in situ hybridization identifies high risk Barrett's patients likely to develop esophageal adenocarcinoma', Diseases of the Esophagus. https://doi.org/10.1111/dote.12372
Brankley, S. M. ; Halling, K. C. ; Jenkins, S. M. ; Timmer, M. R. ; Iyer, Prasad G ; Smyrk, Thomas Christopher ; Barr Fritcher, E. G. ; Voss, J. S. ; Kipp, B. R. ; Campion, M. B. ; Lutzke, L. S. ; Minot, D. M. ; Wang, Kenneth Ke Ning. / Fluorescence in situ hybridization identifies high risk Barrett's patients likely to develop esophageal adenocarcinoma. In: Diseases of the Esophagus. 2015.
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abstract = "Barrett's esophagus (BE) with high-grade dysplasia (HGD) defines a group of individuals at high risk of progression to esophageal adenocarcinoma (EA). Fluorescence in situ hybridization (FISH) has been shown to be useful for the detection of dysplasia and EA in endoscopic brushing specimens from BE patients. The aim of this study was to determine whether FISH in combination with histological findings would further identify more rapid progressors to EA. This is a retrospective cohort study of high-risk patients, having a history of biopsy-confirmed HGD without EA, with an endoscopic brushing specimen analyzed by FISH while undergoing endoscopic surveillance and treatment between April 2003 and October 2010. Brushing specimens were assessed by FISH probes targeting 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2), and 20q13 (ZNF217) and evaluated for the presence of polysomy, defined as multiple chromosomal gains (displaying ≥ 3 signals for ≥ 2 probes). Specimens containing ≥ 4 cells exhibiting polysomy were considered polysomic. HGD was confirmed by at least two experienced gastrointestinal pathologists. Of 245 patients in this study, 93 (38.0{\%}) had a polysomic FISH result and 152 (62.0{\%}) had a non-polysomic FISH result. Median follow-up was 3.6 years (interquartile range [IQR] 2-5 years). Patients with a polysomic FISH result had a significantly higher risk of developing EA within 2 years (14.2{\%}) compared with patients with a non-polysomic FISH result (1.4{\%}, P < 0.001). These findings suggest that a polysomic FISH result in BE patients with simultaneous HGD identifies patients at a higher risk for developing EA compared with those with non-polysomy.",
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AU - Brankley, S. M.

AU - Halling, K. C.

AU - Jenkins, S. M.

AU - Timmer, M. R.

AU - Iyer, Prasad G

AU - Smyrk, Thomas Christopher

AU - Barr Fritcher, E. G.

AU - Voss, J. S.

AU - Kipp, B. R.

AU - Campion, M. B.

AU - Lutzke, L. S.

AU - Minot, D. M.

AU - Wang, Kenneth Ke Ning

PY - 2015

Y1 - 2015

N2 - Barrett's esophagus (BE) with high-grade dysplasia (HGD) defines a group of individuals at high risk of progression to esophageal adenocarcinoma (EA). Fluorescence in situ hybridization (FISH) has been shown to be useful for the detection of dysplasia and EA in endoscopic brushing specimens from BE patients. The aim of this study was to determine whether FISH in combination with histological findings would further identify more rapid progressors to EA. This is a retrospective cohort study of high-risk patients, having a history of biopsy-confirmed HGD without EA, with an endoscopic brushing specimen analyzed by FISH while undergoing endoscopic surveillance and treatment between April 2003 and October 2010. Brushing specimens were assessed by FISH probes targeting 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2), and 20q13 (ZNF217) and evaluated for the presence of polysomy, defined as multiple chromosomal gains (displaying ≥ 3 signals for ≥ 2 probes). Specimens containing ≥ 4 cells exhibiting polysomy were considered polysomic. HGD was confirmed by at least two experienced gastrointestinal pathologists. Of 245 patients in this study, 93 (38.0%) had a polysomic FISH result and 152 (62.0%) had a non-polysomic FISH result. Median follow-up was 3.6 years (interquartile range [IQR] 2-5 years). Patients with a polysomic FISH result had a significantly higher risk of developing EA within 2 years (14.2%) compared with patients with a non-polysomic FISH result (1.4%, P < 0.001). These findings suggest that a polysomic FISH result in BE patients with simultaneous HGD identifies patients at a higher risk for developing EA compared with those with non-polysomy.

AB - Barrett's esophagus (BE) with high-grade dysplasia (HGD) defines a group of individuals at high risk of progression to esophageal adenocarcinoma (EA). Fluorescence in situ hybridization (FISH) has been shown to be useful for the detection of dysplasia and EA in endoscopic brushing specimens from BE patients. The aim of this study was to determine whether FISH in combination with histological findings would further identify more rapid progressors to EA. This is a retrospective cohort study of high-risk patients, having a history of biopsy-confirmed HGD without EA, with an endoscopic brushing specimen analyzed by FISH while undergoing endoscopic surveillance and treatment between April 2003 and October 2010. Brushing specimens were assessed by FISH probes targeting 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2), and 20q13 (ZNF217) and evaluated for the presence of polysomy, defined as multiple chromosomal gains (displaying ≥ 3 signals for ≥ 2 probes). Specimens containing ≥ 4 cells exhibiting polysomy were considered polysomic. HGD was confirmed by at least two experienced gastrointestinal pathologists. Of 245 patients in this study, 93 (38.0%) had a polysomic FISH result and 152 (62.0%) had a non-polysomic FISH result. Median follow-up was 3.6 years (interquartile range [IQR] 2-5 years). Patients with a polysomic FISH result had a significantly higher risk of developing EA within 2 years (14.2%) compared with patients with a non-polysomic FISH result (1.4%, P < 0.001). These findings suggest that a polysomic FISH result in BE patients with simultaneous HGD identifies patients at a higher risk for developing EA compared with those with non-polysomy.

KW - Barrett's esophagus

KW - Cytology

KW - Esophageal adenocarcinoma

KW - FISH

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