Fluorescence in situ hybridization mapping of esophagectomy specimens from patients with Barrett's esophagus with high-grade dysplasia or adenocarcinoma

Shannon M. Brankley, Emily G Barr Fritcher, Thomas Christopher Smyrk, Matthew E. Keeney, Michael B. Campion, Jesse S. Voss, Amy C. Clayton, Kenneth Ke Ning Wang, Lori S. Lutzke, Benjamin R. Kipp, Kevin C. Halling

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12 Citations (Scopus)

Abstract

The progression of intestinal metaplasia to esophageal adenocarcinoma in patients with Barrett's esophagus is partly driven by chromosomal alterations that activate oncogenes and inactivate tumor suppressor genes. The goal of this study was to determine how alterations of 4 frequently affected genes correlate with the range of histopathologic lesions observed in resected esophagi of patients with Barrett's esophagus. Fluorescence in situ hybridization was used to assess 83 tissue sections from 10 Barrett's esophagus esophagogastrectomy specimens for chromosomal alterations of 8q24 (MYC), 9p21 (CDKN2A; alias P16), 17q12 (ERBB2), and 20q13.2 (ZNF217). Histologic lesions assessed included gastric metaplasia (n = 8), intestinal metaplasia (n = 43), low-grade dysplasia (n = 28), high-grade dysplasia (n = 25), and adenocarcinoma (n = 16). Histologic maps showing the correlation between fluorescence in situ hybridization abnormalities and corresponding histology were created for all patients. Chromosomal abnormalities included 9p21 loss, single locus gain, and polysomy. A greater number of chromosomal alterations were detected as the severity of histologic diagnosis increased from intestinal metaplasia to adenocarcinoma. All patients had alterations involving the CDKN2A gene. CDKN2A loss was the only abnormality detected in 20 (47%) of 43 areas of intestinal metaplasia. Polysomy, the most common abnormality in dysplastic epithelium and adenocarcinoma, was observed in 16 (57%) of 28 low-grade dysplasia, 22 (88%) of 25 high-grade dysplasia, and 16 (100%) of 16 adenocarcinoma. The findings of this study improve our understanding of the role that chromosomal instability and alterations of tumor suppressor genes such as CDKN2A and oncogenes such as ERBB2 play in the progression of intestinal metaplasia to adenocarcinoma in patients with Barrett's esophagus.

Original languageEnglish (US)
Pages (from-to)172-179
Number of pages8
JournalHuman Pathology
Volume43
Issue number2
DOIs
StatePublished - Feb 2012

Fingerprint

Esophagectomy
Barrett Esophagus
Metaplasia
Fluorescence In Situ Hybridization
Adenocarcinoma
Tumor Suppressor Genes
Oncogenes
p16 Genes
Chromosomal Instability
Chromosome Aberrations
Esophagus
Stomach
Histology
Epithelium
Genes

Keywords

  • Dysplasia
  • Esophageal cancer
  • FISH
  • Histopathology
  • Intestinal metaplasia

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Brankley, S. M., Fritcher, E. G. B., Smyrk, T. C., Keeney, M. E., Campion, M. B., Voss, J. S., ... Halling, K. C. (2012). Fluorescence in situ hybridization mapping of esophagectomy specimens from patients with Barrett's esophagus with high-grade dysplasia or adenocarcinoma. Human Pathology, 43(2), 172-179. https://doi.org/10.1016/j.humpath.2011.04.018

Fluorescence in situ hybridization mapping of esophagectomy specimens from patients with Barrett's esophagus with high-grade dysplasia or adenocarcinoma. / Brankley, Shannon M.; Fritcher, Emily G Barr; Smyrk, Thomas Christopher; Keeney, Matthew E.; Campion, Michael B.; Voss, Jesse S.; Clayton, Amy C.; Wang, Kenneth Ke Ning; Lutzke, Lori S.; Kipp, Benjamin R.; Halling, Kevin C.

In: Human Pathology, Vol. 43, No. 2, 02.2012, p. 172-179.

Research output: Contribution to journalArticle

Brankley, SM, Fritcher, EGB, Smyrk, TC, Keeney, ME, Campion, MB, Voss, JS, Clayton, AC, Wang, KKN, Lutzke, LS, Kipp, BR & Halling, KC 2012, 'Fluorescence in situ hybridization mapping of esophagectomy specimens from patients with Barrett's esophagus with high-grade dysplasia or adenocarcinoma', Human Pathology, vol. 43, no. 2, pp. 172-179. https://doi.org/10.1016/j.humpath.2011.04.018
Brankley, Shannon M. ; Fritcher, Emily G Barr ; Smyrk, Thomas Christopher ; Keeney, Matthew E. ; Campion, Michael B. ; Voss, Jesse S. ; Clayton, Amy C. ; Wang, Kenneth Ke Ning ; Lutzke, Lori S. ; Kipp, Benjamin R. ; Halling, Kevin C. / Fluorescence in situ hybridization mapping of esophagectomy specimens from patients with Barrett's esophagus with high-grade dysplasia or adenocarcinoma. In: Human Pathology. 2012 ; Vol. 43, No. 2. pp. 172-179.
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abstract = "The progression of intestinal metaplasia to esophageal adenocarcinoma in patients with Barrett's esophagus is partly driven by chromosomal alterations that activate oncogenes and inactivate tumor suppressor genes. The goal of this study was to determine how alterations of 4 frequently affected genes correlate with the range of histopathologic lesions observed in resected esophagi of patients with Barrett's esophagus. Fluorescence in situ hybridization was used to assess 83 tissue sections from 10 Barrett's esophagus esophagogastrectomy specimens for chromosomal alterations of 8q24 (MYC), 9p21 (CDKN2A; alias P16), 17q12 (ERBB2), and 20q13.2 (ZNF217). Histologic lesions assessed included gastric metaplasia (n = 8), intestinal metaplasia (n = 43), low-grade dysplasia (n = 28), high-grade dysplasia (n = 25), and adenocarcinoma (n = 16). Histologic maps showing the correlation between fluorescence in situ hybridization abnormalities and corresponding histology were created for all patients. Chromosomal abnormalities included 9p21 loss, single locus gain, and polysomy. A greater number of chromosomal alterations were detected as the severity of histologic diagnosis increased from intestinal metaplasia to adenocarcinoma. All patients had alterations involving the CDKN2A gene. CDKN2A loss was the only abnormality detected in 20 (47{\%}) of 43 areas of intestinal metaplasia. Polysomy, the most common abnormality in dysplastic epithelium and adenocarcinoma, was observed in 16 (57{\%}) of 28 low-grade dysplasia, 22 (88{\%}) of 25 high-grade dysplasia, and 16 (100{\%}) of 16 adenocarcinoma. The findings of this study improve our understanding of the role that chromosomal instability and alterations of tumor suppressor genes such as CDKN2A and oncogenes such as ERBB2 play in the progression of intestinal metaplasia to adenocarcinoma in patients with Barrett's esophagus.",
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