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Comprehensive Analysis of Barrett’s Esophagus: Focused on Carcinogenic Potential for Barrett’s Cancer in Japanese Patients

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Abstract

Background/Aim

Barrett’s esophagus (BE) is a precursor of esophageal adenocarcinoma (EAC). Therefore, an accurate diagnosis of BE is important for the subsequent follow-up and early detection of EAC. However, the definitions of BE have not been standardized worldwide; columnar-lined epithelium (CLE) without intestinal metaplasia (IM) and/or < 1 cm is not diagnosed as BE in most countries. This study aimed to clarify the malignant potential of CLE without IM and/or < 1 cm genetically.

Method

A total of 96 consecutive patients (including nine patients with EAC) who had CLE were examined. Biopsies for CLE were conducted, and patients were divided into those with IM and > 1 cm (Group A) and those without IM and/or < 1 cm (Group B). Malignant potential was assessed using immunochemical staining for p53. Moreover, causative genes were examined using next-generation sequencing (NGS) on ten patients without Helicobacter pylori infection and without atrophic gastritis.

Result

Of the 96 patients, 66 were in Group B. The proportion of carcinoma/dysplasia in Group A was significantly higher than that in Group B (26.7% in Group A and 1.5% in Group B; p < 0.01). However, one EAC patient was found in Group B. In the immunostaining study for non-EAC patients, an abnormal expression of p53 was not observed in Group A, whereas p53 loss was observed in three patients (4.6%) in Group B. In the NGS study, a TP53 mutation was found in Group B.

Conclusion

CLE without IM and/or < 1 cm has malignant potential. This result suggests that patients with CLE as well as BE need follow-up.

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Abbreviations

BE:

Barrett’s esophagus

CLE:

Columnar-lined epithelium

EAC:

Esophageal adenocarcinoma

IM:

Intestinal metaplasia

SCJ:

Squamocolumnar junction

PVs:

Palisade vessels

LSBE:

Long-segment Barrett’s esophagus

SSBE:

Short-segment Barrett’s esophagus

USSBE:

Ultrashort segment Barrett’s esophagus

NGS:

Next-generation sequencing

SD:

Standard deviation

ESCC:

Esophageal squamous cell carcinoma

References

  1. Spechler SJ, Goyal RK. Barrett’s esophagus. N Engl J Med. 1986;315:362–371.

    Article  CAS  Google Scholar 

  2. Barrett NR. The lower esophagus lined by columnar epithelium. Surgery. 1957;41:881–894.

    CAS  PubMed  Google Scholar 

  3. 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.

    Article  Google Scholar 

  4. Everhart JE, Ruhl CE. Burden of digestive diseases in the United States part I: overall and upper gastrointestinal diseases. Gastroenterology. 2009;136:376–386.

    Article  Google Scholar 

  5. Caygill CP, Royston C, Charlett A, et al. Mortality in Barrett’s esophagus: three decades of experience at a single center. Endoscopy. 2012;44:892–898.

    Article  CAS  Google Scholar 

  6. Shaheen NJ, Falk GW, Iyer PG, et al. American College of Gastroenterology. ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus. Am J Gastroenterol. 2016;111:30–50.

    Article  CAS  Google Scholar 

  7. Japan Esophageal Society. Japanese Classification of Esophageal Cancer, 11th Edition. Esophagus. 2017; 14: 37–65.

  8. Bhat S, Coleman HG, Yousef F, et al. Risk of malignant progression in Barrett’s esophagus patients: results from a large population-based study. J Natl Cancer Inst. 2011;103:1049–1057.

    Article  Google Scholar 

  9. Younes M, Brown K, Lauwers GY, et al. p53 protein accumulation predicts malignant progression in Barrett’s metaplasia: a prospective study of 275 patients. Histopathology. 2017;71:27–33.

    Article  Google Scholar 

  10. Younes M, Ertan A, Lechago LV, et al. P53 Protein accumulation is a specific marker of malignant potential in Barrett’s metaplasia. Dig Dis Sci. 1997;42:697–701. https://doi.org/10.1023/A:1018828207371.

    Article  CAS  PubMed  Google Scholar 

  11. Contino G, Vaughan TL, Whiteman D, et al. The evolving genomic landscape of Barrett’s esophagus and esophageal adenocarcinoma. Gastroenterology. 2017;153:657–673.

    Article  Google Scholar 

  12. Stachler MD, Camarda ND, Deitrick C, et al. Detection of mutations in Barrett’s esophagus before progression to high-grade dysplasia or adenocarcinoma. Gastroenterology. 2018;155:156–167.

    Article  CAS  Google Scholar 

  13. Amano Y, Ishimura N, Furuta K, et al. Which landmark results in a more consistent diagnosis of Barrett’s esophagus, the gastric folds or the palisade vessels? Gastrointest Endosc. 2006;64:206–211.

    Article  Google Scholar 

  14. Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The Updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Pathol. 1996;20:1161–1181.

    Article  CAS  Google Scholar 

  15. Timmer MR, Martinez P, Lau CT, et al. Derivation of genetic biomarkers for cancer risk stratification in Barrett’s oesophagus: a prospective cohort study. Gut. 2016;65:1602–1610.

    Article  CAS  Google Scholar 

  16. Thota PN, Vennalaganti P, Vennelaganti S, et al. Low risk of high-grade dysplasia or esophageal adenocarcinoma among patients with Barrett’s esophagus less than 1 cm (irregular z line) within 5 years of index endoscopy. Gastroenterology. 2017;152:987–992.

    Article  Google Scholar 

  17. Jung KW, Talley NJ, Romero Y, et al. Epidemiology and natural history of intestinal metaplasia of the gastroesophageal junction and Barrett’s esophagus: a population-based study. Am J Gastroenterol. 2011;106:1447–1455.

    Article  Google Scholar 

  18. Streppel MM, Lata S, DelaBastide M, et al. Next-generation sequencing of endoscopic biopsies identifies ARID1A as a tumor-suppressor gene in Barrett’s esophagus. Oncogene. 2014;33:347–357.

    Article  CAS  Google Scholar 

  19. Rabinovitch PS, Reid BJ, Haggitt RC, et al. Progression to cancer in Barrett’s esophagus is associated with genomic instability. Lab Invest. 1988;60:65–71.

    Google Scholar 

  20. Yokoyama A, Kakiuchi N, Yoshizato T, et al. Age-related remodelling of oesophageal epithelia by mutated cancer drivers. Nature. 2019;565:312–317.

    Article  CAS  Google Scholar 

  21. Altaf K, Xiong JJ, la Iglesia D, et al. Meta-analysis of biomarkers predicting risk of malignant progression in Barrett’s oesophagus. Br J Surg. 2017;104:493–502.

    Article  CAS  Google Scholar 

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Authors and Affiliations

Authors

Contributions

K.I. wrote paper. K.O., T.M., Y.H., K.A., T.K., M.N., K.M., H.M., and M.A. designed study and analyzed data. N.A., Y.O., K.S., and D.M. performed endoscopy and analyzed data. J.K., O.Y., M.O., and N.K. study supervision.

Corresponding author

Correspondence to Kenichiro Okimoto.

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All authors were involved in the final approval of the version of the manuscript submitted and have agreed to be accountable for all aspects of the work. There is no relevant conflict of interest or disclosures, including financial and material support for the research and work in this manuscript.

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Ishikawa, K., Okimoto, K., Matsumura, T. et al. Comprehensive Analysis of Barrett’s Esophagus: Focused on Carcinogenic Potential for Barrett’s Cancer in Japanese Patients. Dig Dis Sci 66, 2674–2681 (2021). https://doi.org/10.1007/s10620-020-06563-1

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