CC BY-NC-ND 4.0 · Endosc Int Open 2021; 09(03): E348-E355
DOI: 10.1055/a-1326-1533
Original article

TissueCypher Barrett’s esophagus assay impacts clinical decisions in the management of patients with Barrett’s esophagus

David L. Diehl
1   Department of Gastroenterology, Geisinger Health System, Danville, Pennsylvania, United States
Harshit S. Khara
1   Department of Gastroenterology, Geisinger Health System, Danville, Pennsylvania, United States
Nasir Akhtar
1   Department of Gastroenterology, Geisinger Health System, Danville, Pennsylvania, United States
Rebecca J. Critchley-Thorne
2   Cernostics, Inc., Pittsburgh, Pennsylvania, United States
› Author Affiliations


Background and study aims The TissueCypher Barrett’s Esophagus Assay is a novel tissue biomarker test, and has been validated to predict progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett’s esophagus (BE). The aim of this study was to evaluate the impact of TissueCypher on clinical decision-making in the management of BE.

Patients and methods TissueCypher was ordered for 60 patients with non-dysplastic (ND, n = 18) BE, indefinite for dysplasia (IND, n = 25), and low-grade dysplasia (LGD, n = 17). TissueCypher reports a risk class (low, intermediate or high) for progression to HGD or EAC within 5 years. The impact of the test results on BE management decisions was assessed.

Results Fifty-two of 60 patients were male, mean age 65.2 ± 11.8, and 43 of 60 had long segment BE. TissueCypher results impacted 55.0 % of management decisions. In 21.7 % of patients, the test upstaged the management approach, resulting in endoscopic eradication therapy (EET) or shorter surveillance interval. The test downstaged the management approach in 33.4 % of patients, leading to surveillance rather than EET. In the subset of patients whose management plan was changed, upstaging was associated with a high-risk TissueCypher result, and downstaging was associated with a low-risk result (P < 0.0001).

Conclusions TissueCypher was used as an adjunct to support a surveillance-only approach in 33.4 % of patients. Upstaging occurred in 21.7 % of patients, leading to therapeutic intervention or increased surveillance. These results indicate that the TissueCypher test may enable physicians to target EET for TissueCypher high-risk BE patients, while reducing unnecessary procedures in TissueCypher low-risk patients.

Publication History

Received: 30 July 2020

Accepted: 21 October 2020

Article published online:
18 February 2021

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  • References

  • 1 Thrift AP. Barrettʼs Esophagus and Esophageal Adenocarcinoma: How Common Are They Really?. Dig Dis Sci 2018; 63: 1988-1996
  • 2 Ferlay J, Colombet M, Soerjomataram I. et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer 2018; 144: 1941-1953
  • 3 Spechler SJ, Sharma P, Souza RF. et al. American Gastroenterological Association medical position statement on the management of Barrettʼs esophagus. Gastroenterology 2011; 140: 1084-1091
  • 4 Shaheen NJ, Falk GW, Iyer PG. et al. ACG Clinical Guideline: Diagnosis and Management of Barrettʼs Esophagus. Am J Gastroenterol 2015; 111: 30-50
  • 5 Qumseya B, Sultan S, Bain P. et al. ASGE guideline on screening and surveillance of Barrettʼs esophagus. Gastrointest Endosc 2019; 90: 335-359 e332
  • 6 Montgomery E, Bronner MP, Goldblum JR. et al. Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation. Hum Pathol 2001; 32: 368-378
  • 7 Vennalaganti P, Kanakadandi V, Goldblum JR. et al. Discordance among pathologists in the United States and Europe in diagnosis of low-grade dysplasia for patients with Barrettʼs esophagus. Gastroenterology 2017; 152: 564-570 e564
  • 8 Qumseya BJ, Wani S, Desai M. et al. Adverse events after radiofrequency ablation in patients with Barrettʼs esophagus: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2016; 14: 1086-1095 e1086
  • 9 Goldblum JR. Controversies in the diagnosis of Barrett esophagus and Barrett-related dysplasia: one pathologistʼs perspective. Arch Pathol Lab Med 2010; 134: 1479-1484
  • 10 Krishnamoorthi R, Singh S, Ragunathan K. et al. Factors associated with progression of Barrettʼs esophagus: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2018; 16: 1046-1055 e1048
  • 11 Davison JM, Shah MB, Deitrick C. et al. Low-grade dysplasia diagnosis ratio and progression metrics identify variable Barrettʼs esophagus risk stratification proficiency in independent pathology practices. Gastrointest Endosc 2018; 88: 807-815 e802
  • 12 Krishnamoorthi R, Mohan BP, Jayaraj M. et al. Risk of progression in Barrettʼs esophagus indefinite for dysplasia: a systematic review and meta-analysis. Gastrointest Endosc 2020; 91: 3-10 e13
  • 13 Wani S, Falk G, Hall M. et al. Patients with nondysplastic Barrettʼs esophagus have low risks for developing dysplasia or esophageal adenocarcinoma. Clin Gastroenterol Hepatol 2011; 9: 220-227
  • 14 Desai TK, Krishnan K, Samala N. et al. The incidence of oesophageal adenocarcinoma in non-dysplastic Barrettʼs oesophagus: a meta-analysis. Gut 2012; 61: 970-976
  • 15 Anaparthy R, Gaddam S, Kanakadandi V. et al. Association between length of Barrettʼs esophagus and risk of high-grade dysplasia or adenocarcinoma in patients without dysplasia. Clin Gastroenterol Hepatol 11: 1430-1436
  • 16 Kambhampati S, Tieu AH, Luber B. et al. Risk factors for grogression of Barrettʼs esophagus to high grade dysplasia and esophageal adenocarcinoma. Sci Rep 2020; 10: 4899
  • 17 Thrift AP, Kunzmann AT. Time to Tailor surveillance intervals of nondysplastic Barrettʼs esophagus according to segment length and persistence over multiple endoscopies. Clin Gastroenterol Hepatol 2018; 17: 832-834
  • 18 Shaheen NJ, Green B, Medapalli RK. et al. The perception of cancer risk in patients with prevalent Barrettʼs esophagus enrolled in an endoscopic surveillance program. Gastroenterology 2005; 129: 429-436
  • 19 Wani S, Williams JL, Komanduri S. et al. Over-utilization of repeat upper endoscopy in patients with non-dysplastic Barrettʼs esophagus: a quality registry study. Am J Gastroenterol 2019; 144: 1256-1264
  • 20 Critchley-Thorne RJ, Duits LC, Prichard JW. et al. A Tissue Systems Pathology Assay for High-Risk Barrettʼs Esophagus. Cancer Epidemiol Biomarkers Prev 2016; 25: 958-968
  • 21 Critchley-Thorne RJ, Davison JM, Prichard JW. et al. A tissue systems pathology test detects abnormalities associated with prevalent high-grade dysplasia and esophageal cancer in Barrettʼs esophagus. Cancer Epidemiol Biomarkers Prev 2017; 26: 240-248
  • 22 Davison JM, Goldblum J, Grewal US. et al. Independent blinded validation of a tissue systems pathology test to predict progression in patients with Barrettʼs esophagus. Am J Gastroenterol 2020; 115: 843-852
  • 23 Frei NF, Konte K, Bossart EA. et al. Independent Validation of tissuecypher to predict future progression in non-dysplastic Barrett’s esophagus: a spatial-temporal analysis. Clin Transl Gastroenterol 2020; 11: e00244
  • 24 Frei NF, Khoshiwal AM, Konte K. et al. A Tissue systems pathology test objectively risk stratifies Barrett’s esophagus patients with low-grade dysplasia. Am J Gastroenterol 2020; DOI: 10.14309/ajg.0000000000001037.
  • 25 Prichard JW, Davison JM, Campbell BB. et al. TissueCypher: A systems biology approach to anatomic pathology. J Pathol Informat 2015; 6: 48
  • 26 DeWard A, Critchley-Thorne RJ. Systems Biology approaches in cancer pathology. Methods Mol Biol 2018; 1711: 261-273
  • 27 Hao J, Critchley-Thorne RJ, Diehl DL. et al. A cost-effectiveness analysis of an adenocarcinoma risk prediction multi-biomarker assay for patients with Barrett’s esophagus. ClinicoEcon Outcomes Res 2019; 11: 623-635
  • 28 Lash RH, Deas Jr TM , Wians Jr FH . Healthcare cost of over-diagnosis of low-grade dysplasia in Barrettʼs esophagus. Adv Ther 2016; 33: 684-697
  • 29 Carlson JJ, Roth JA. The impact of the Oncotype Dx breast cancer assay in clinical practice: a systematic review and meta-analysis. Breast Cancer Res Treat 2013; 141: 13-22
  • 30 Akerley WL, Arnaud AM, Reddy B. et al. Impact of a multivariate serum-based proteomic test on physician treatment recommendations for advanced non-small-cell lung cancer. Curr Med Res Opin 2017; 33: 1091-1097