A Multicenter Study of a Fluorescence In Situ Hybridization Probe Set for Diagnosing High-Grade Dysplasia and Adenocarcinoma in Barrett's Esophagus

John M Poneros¹, Adam S Faye², Emily G Barr Fritcher³, Ananda Sen^{4

5}, Sharmila Anandasabapathy⁶, Robert S Bresalier⁷, Norman Marcon^{8

9}, D Kim Turgeon^{10

11}, Henry Appelman¹², Daniel Normolle¹³, Larry E Morrison^{14

15}, Dean E Brenner^{10

16}, Kevin C Halling³

Affiliations

¹ Department of Gastroenterology, Columbia University Medical Center, 161 Fort Washington Avenue, Suite 862, New York, NY, 10032, USA. jmp14@cumc.columbia.edu.
² Department of Internal Medicine, Columbia University Medical Center, 177 Fort Washington Avenue, Milstein 6C-12, New York, NY, 10032, USA.
³ Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First SW, Rochester, MN, 55905, USA.
⁴ Department of Biostatistics, University of Michigan Medical Center, Ann Arbor, MI, USA.
⁵ Department of Family Medicine, University of Michigan Medical School, 1018 Fuller St., Ann Arbor, MI, 48104, USA.
⁶ Department of Gastroenterology, Baylor College of Medicine, Baylor St. Luke's Medical Center Clinic, 7200 Cambridge Street Suite 10C, Houston, TX, 77030, USA.
⁷ Department of Gastroenterology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1466, Houston, TX, 77030, USA.
⁸ Department of Gastroenterology, University of Toronto, Toronto, ON, Canada.
⁹ St. Michael's Hospital, University of Toronto, 30 Bond Street, 16-062 Cardinal Carter South Wing, Toronto, ON, M5B 1W8, Canada.
¹⁰ Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
¹¹ Department of Gastroenterology, University of Michigan Health System, Taubman Center Floor 3, Reception D, 1500 E Medical Center Dr, Ann Arbor, MI, 48109, USA.
¹² Department of Pathology, University of Michigan Medical Center, 1301 Catherine St., Ann Arbor, MI, 48109, USA.
¹³ Department of Biostatistics, University of Pittsburgh Cancer Institute, 201 North Craig Street, Sterling Plaza Suite 325, Pittsburgh, PA, 15213, USA.
¹⁴ Abbott Molecular, Inc., Des Plaines, IL, USA.
¹⁵ Ventana Medical Systems Inc., 1910 E. Innovation Park Dr., Tucson, AZ, 85755, USA.
¹⁶ Department of Pharmacology, University of Michigan Medical Center, 1500 E Medical Center Dr #2150, Ann Arbor, MI, 48109, USA.

PMID: 28265829
PMCID: PMC6052443
DOI: 10.1007/s10620-017-4517-y

Multicenter Study

A Multicenter Study of a Fluorescence In Situ Hybridization Probe Set for Diagnosing High-Grade Dysplasia and Adenocarcinoma in Barrett's Esophagus

John M Poneros et al. Dig Dis Sci. 2017 May.

. 2017 May;62(5):1216-1222.

doi: 10.1007/s10620-017-4517-y. Epub 2017 Mar 6.

Authors

Affiliations

¹ Department of Gastroenterology, Columbia University Medical Center, 161 Fort Washington Avenue, Suite 862, New York, NY, 10032, USA. jmp14@cumc.columbia.edu.
² Department of Internal Medicine, Columbia University Medical Center, 177 Fort Washington Avenue, Milstein 6C-12, New York, NY, 10032, USA.
³ Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First SW, Rochester, MN, 55905, USA.
⁴ Department of Biostatistics, University of Michigan Medical Center, Ann Arbor, MI, USA.
⁵ Department of Family Medicine, University of Michigan Medical School, 1018 Fuller St., Ann Arbor, MI, 48104, USA.
⁶ Department of Gastroenterology, Baylor College of Medicine, Baylor St. Luke's Medical Center Clinic, 7200 Cambridge Street Suite 10C, Houston, TX, 77030, USA.
⁷ Department of Gastroenterology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1466, Houston, TX, 77030, USA.
⁸ Department of Gastroenterology, University of Toronto, Toronto, ON, Canada.
⁹ St. Michael's Hospital, University of Toronto, 30 Bond Street, 16-062 Cardinal Carter South Wing, Toronto, ON, M5B 1W8, Canada.
¹⁰ Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
¹¹ Department of Gastroenterology, University of Michigan Health System, Taubman Center Floor 3, Reception D, 1500 E Medical Center Dr, Ann Arbor, MI, 48109, USA.
¹² Department of Pathology, University of Michigan Medical Center, 1301 Catherine St., Ann Arbor, MI, 48109, USA.
¹³ Department of Biostatistics, University of Pittsburgh Cancer Institute, 201 North Craig Street, Sterling Plaza Suite 325, Pittsburgh, PA, 15213, USA.
¹⁴ Abbott Molecular, Inc., Des Plaines, IL, USA.
¹⁵ Ventana Medical Systems Inc., 1910 E. Innovation Park Dr., Tucson, AZ, 85755, USA.
¹⁶ Department of Pharmacology, University of Michigan Medical Center, 1500 E Medical Center Dr #2150, Ann Arbor, MI, 48109, USA.

PMID: 28265829
PMCID: PMC6052443
DOI: 10.1007/s10620-017-4517-y

Abstract

Background and aims: Preliminary single-institution data suggest that fluorescence in situ hybridization (FISH) may be useful for detecting high-grade dysplasia (HGD) and esophageal adenocarcinoma (EA) in patients with Barrett's esophagus (BE). This multicenter study aims to validate the measurement of polysomy (gain of at least two loci) by FISH as a way to discriminate degrees of dysplasia in BE specimens.

Methods: Tissue specimens were collected from four different hospitals and read by both the local pathology department ("Site diagnosis") and a single central pathologist ("Review diagnosis") at a separate institution. The specimens then underwent FISH analysis using probes 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2), and 20q13 (ZNF217) for comparison. A total of 46 non-BE, 42 non-dysplastic specialized intestinal metaplasia (SIM), 23 indefinite-grade dysplasia (IGD), 10 low-grade dysplasia (LGD), 29 HGD, and 42 EA specimens were analyzed.

Results: We found that polysomy, as detected by FISH, was the predominant chromosomal abnormality present as dysplasia increased. Polysomy was also the best predictor for the presence of dysplasia or EA when comparing its area under the curve to that of other FISH abnormalities. We observed that if at least 10% of cells had polysomy within a specimen, the FISH probe was able to differentiate between EA/HGD and the remaining pathologies with a sensitivity of 80% and a specificity of 88%.

Conclusions: This study demonstrates that using FISH to determine the percentage of cells with polysomy can accurately and objectively aid in the diagnosis of HGD/EA in BE specimens.

Keywords: Barrett’s esophagus; Dysplasia; Endoscopy; FISH; Histopathology; Polysomy.

PubMed Disclaimer

Figures

**Fig. 1**
Predominant FISH abnormality per histologic classification. If more than one FISH abnormality was detected in a specimen, the most predominant (highest percentage) was used for this analysis

See this image and copyright information in PMC

References

1. Devesa SS, Blot WJ, Fraumeni JF., Jr Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer. 1998;83:2049–2053. - PubMed
1. Polednak AP. Trends in survival for both histologic types of esophageal cancer in US surveillance, epidemiology and end results areas. Int J Cancer. 2003;105:98–100. - PubMed
1. Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst. 2005;97:142–146. - PubMed
1. Zhang Y. Epidemiology of esophageal cancer. World J Gastroenterol. 2013;19:5598–5606. - PMC - PubMed
1. Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349:2241–2252. - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations
Medical
- MedlinePlus Health Information
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

A Multicenter Study of a Fluorescence In Situ Hybridization Probe Set for Diagnosing High-Grade Dysplasia and Adenocarcinoma in Barrett's Esophagus

Affiliations

A Multicenter Study of a Fluorescence In Situ Hybridization Probe Set for Diagnosing High-Grade Dysplasia and Adenocarcinoma in Barrett's Esophagus

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials

Miscellaneous