Skip to main content

Advertisement

SpringerLink
Log in

Multilayered Epithelium May Be Found in Patients With Barrett’s Epithelium and Dysplasia or Adenocarcinoma

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

To determine if multilayered epithelium (MLE) is a useful prognostic indicator for a benign natural history of Barrett’s epithelium, we evaluated endoscopic biopsies from patients with Barrett’s epithelium without and with dysplasia and/or adenocarcinoma and from non-Barrett's controls for the presence of MLE. MLE was found in 6% of non-Barrett's controls, 30% of Barrett’s patients with no dysplasia, and 14% of Barrett's patients with dysplasia and/or adenocarcinoma. MLE was significantly associated with shorter lengths of Barrett’s epithelium in both Barrett’s groups. Three of 5 photodynamic therapy patients were noted to develop MLE after therapy. MLE may be found in patients with dysplasia and/or adenocarcinoma and after photodynamic therapy; its presence is not useful as a prognostic indicator for a more benign course of Barrett’s. This study confirms that MLE is significantly associated with shorter lengths of Barrett’s epithelium.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Spechler SJ, Goyal RK (1996) The columnar lined esophagus, intestinal metaplasia and Norman Barrett. Gastroenterology 110:614–621

    Article  PubMed  CAS  Google Scholar 

  2. Falk GW (2002) Barrett’s esophagus. Gastroenterology 122:1569–1591

    Article  Google Scholar 

  3. Vaezi MF, Singh S, Richter JE (1995) Role of acid and duodenogastric reflux in esophageal mucosal injury: A review of animal and human studies. Gastroenterology 108:1897–1907

    Article  PubMed  CAS  Google Scholar 

  4. Menges M, Muller M, Zeitz M (2001) Increased acid and bile reflux in Barrett’s esophagus compared to reflux esophagitis, and effect of proton pump inhibitor therapy. Am J Gastroenterol 96:331–337

    Article  PubMed  CAS  Google Scholar 

  5. Triadafilopoulos G (2001) Acid and bile reflux in Barrett’s esophagus: A tale of two evils. Gastroenterology 121:1502–1506

    PubMed  CAS  Google Scholar 

  6. Winters C Jr, Spurling TJ, Chobanian SJ, Curtis DJ, Esposito RL, Hacker III, JF, Johnson DA, Cruess DF, Cotelingam JD, Gurney MS, Cattau EL Jr (1987) Barrett’s esophagus. A prevalent occult complication of gastroesophageal reflux disease. Gastroenterology 92:118–124

    PubMed  Google Scholar 

  7. Pera M, Cameron AJ, Trastek VF, Carpenter HA, Zinsmeister AR (1993) Increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction. Gastroenterology 104:510–513

    PubMed  CAS  Google Scholar 

  8. Cameron AJ, Lomboy CT, Pera M, Carpenter HA (1995) Adenocarcinoma of the esophagogastric junction and Barrett’s esophagus. Gastroenterology 109:1541–1546

    Article  PubMed  CAS  Google Scholar 

  9. O’Connor JB, Falk GW, Richter JE (1999) The incidence of adenocarcinoma and dysplasia in Barrett’s Esophagus: Report on the Cleveland Clinic Barrett's Esophagus Registry. Am J Gastroenterol 94:2037–2042

    PubMed  CAS  Google Scholar 

  10. Drewitz DJ, Sampliner RE, Garewal HS (1997) The incidence of adenocarcinoma in Barrett’s esophagus: A prospective study of 170 patients followed 4.8 years. Am J Gastroenterol 92:212–221

    PubMed  CAS  Google Scholar 

  11. Provenzale D, Schmitt C, Wong JB (1999) Barrett’s esophagus: A new look at surveillance based on emerging estimates of cancer risk. Am J Gastroenterol 94:2043–2053

    Article  PubMed  CAS  Google Scholar 

  12. Lagergren J, Bergstrom R, Lindgren A, Nyren O (1999) Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 340:825–831

    Article  PubMed  CAS  Google Scholar 

  13. Shaheen N, Ransohoff DF (2002) Gastroesophageal reflux, Barrett esophagus, and esophageal cancer: Scientific review. JAMA 287:1972–1981

    Article  PubMed  Google Scholar 

  14. Shaheen NJ, Crosby MA, Bozymski EM, Sandler RS (2000) Is there publication bias in the reporting of cancer risk in Barrett’s esophagus? Gastroenterology 119:333–338

    Article  PubMed  CAS  Google Scholar 

  15. Peters FTM, Ganesh S, Kuipers EJ, Sluiter WJ, Klinkenberg-Knol EC, Lamers CBHW, Kleibeuker JH (1999) Endoscopic regression of Barrett’s oesophagus during omeprazole treatment: A randomized double blind study. Gut 45:489–494

    Article  PubMed  CAS  Google Scholar 

  16. Ye W, Chow WH, Lagergren J, Yin L, Nyren O (2001) Risk of adenocarcinomas of the esophagus and gastric cardia in patients with gastroesophageal reflux disease and after antireflux surgery. Gastroenterology 121:1286–1293

    Article  PubMed  CAS  Google Scholar 

  17. Carlson N, Lechago J, Richter J, Sampliner RE, Peterson L, Santella RM, Goldblum JR, Falk GW, Ertan A, Younes M (2002) Acid suppression therapy may not alter malignant progression in Barrett’s metaplasia showing p53 protein accumulation. Am J Gastroenterol 97:1340–1345

    Article  PubMed  CAS  Google Scholar 

  18. Katzka DA (2002) Barrett’s esophagus: Surveillance and treatment. Gastroenterol Clin North Am 31:481–497

    Article  PubMed  Google Scholar 

  19. McDonald ML, Trastek VF, Allen MS (1996) Barrett’s esophagus: Does an antireflux procedure reduce the need for endoscopic surveillance? J Thorac Cardiovasc Surg 111:1135–1140

    Article  PubMed  CAS  Google Scholar 

  20. Spechler SJ, Lee E, Ahnen D, Goyal RK, Hirano I, Ramirez F, Raufman JP, Sampliner R, Schnell T, Sontag S, Vlahcevic ZR, Young R, Williford W (2001) Long term outcome of medical and surgical therapies for gastroesophageal reflux disease: Followup of a randomized controlled trial. JAMA 285:2331–2338

    Article  PubMed  CAS  Google Scholar 

  21. Parrilla P, Martinez de Haro LF, Ortiz A, Munitiz V, Molina J, Bermejo J, Canteras M (2003) Long-term results of a randomized prospective study comparing medical and surgical treatment of Barrett’s esophagus. Ann Surg 237:291–298

    Article  PubMed  Google Scholar 

  22. Cohen S, Parkman HP (1999) Heartburn: A serious symptom.N Engl J Med 340:878–879

    Article  PubMed  CAS  Google Scholar 

  23. Fitzgerald RC, Lascar R, Triadafilopoulos G (2001) Barrett’s oesophagus, dysplasia and pharmacologic acid suppression. Aliment Pharmacol Ther 15:269–276

    Article  PubMed  CAS  Google Scholar 

  24. Jankowski JA, Wright NA, Meltzer SJ, Triadafilopoulos G, Geboes K, Casson AG, Kerr D, Young LS (1999) Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. Am J Pathol 154:965–973

    PubMed  CAS  Google Scholar 

  25. Bremner CG, Lynch VP, Ellis FJ Jr (1970) Barrett’s esophagus: Congenital or acquired? An experimental study of esophageal mucosal regeneration in the dog. Surgery 68:209–216

    PubMed  CAS  Google Scholar 

  26. Gillen P, Keeling P, Byrne PJ, West AB, Hennessy TPJ (1988) Experimental columnar metaplasia in the canine oesophagus. Br J Surg 75:113–115

    PubMed  CAS  Google Scholar 

  27. Li H, Walsh TN, O’Dowd G, Gillen P, Byrne PJ, Hennessy TPJ (1994) Mechanisms of columnar metaplasia and squamous regeneration in experimental Barrett's esophagus. Surgery 115:176–181

    PubMed  CAS  Google Scholar 

  28. Sbarbati A, Faccioli N, Ricci F, Merigo F, Benati D, Castaldini G, Cordiano C, Osculati F (2002) Ultrastructural phenotype of “intestinal-type” cells in columnar-lined esophagus. Ultrastruct Pathol 26:107–111

    Article  PubMed  CAS  Google Scholar 

  29. Shields, HM, Zwas F, Antonioli DA, Doos WG, Kim S, Spechler SJ (1993) Detection by scanning electron microscopy of a distinctive esophageal surface cell at the junction of squamous and Barrett’s epithelium. Dig Dis Sci 38:97–108

    Article  PubMed  CAS  Google Scholar 

  30. Boch JA, Shields HM, Antonioli DA, Zwas F, Sawhney RA, Trier JS (1997) Distribution of cytokeratin markers in Barrett’s specialized columnar epithelium. Gastroenterology 112:760–765

    Article  PubMed  CAS  Google Scholar 

  31. Glickman JN, Chen Y, Wang HH, Antonioli DA, Odze RD (2001) Phenotypic characteristics of a distinctive multilayered epithelium suggests that it is a precursor in the development of Barrett’s esophagus. Am J Surg Pathol 25:569–578

    Article  PubMed  CAS  Google Scholar 

  32. Glickman JN, Yang A, Shahsafaei A, McKeon F, Odze RD (2001) Expression of p53-related protein p63 in the gastrointestinal tract and in esophageal metaplastic and neoplastic disorders. Hum Pathol 32:1157–1165

    Article  PubMed  CAS  Google Scholar 

  33. Shields HM, Rosenberg SJ, Zwas FR, Ransil BJ, Lembo AJ, Odze R (2001) Prospective evaluation of multilayered epithelium in Barrett’s esophagus. Am J Gastroenterol 96:3268–3273

    Article  PubMed  CAS  Google Scholar 

  34. Menke-Pluymers MBE, Hop WCJ, Dees J, Van Blankenstein M, Tilanus HW (1993) Risk factors for the development of an adenocarcinoma in the columnar-lined (Barrett) esophagus. The Rotterdam Esophageal Tumor Study Group Cancer 72:1155–1158

    Article  PubMed  CAS  Google Scholar 

  35. Rudolph RE, Vaughan TL, Storer BE, Haggitt RC, Rabinovitch PS, Levine DS, Reid BJ (2000) Effect of segment length on risk for neoplastic progression in patients with Barrett esophagus. Ann Intern Med 132:612–620

    Google Scholar 

  36. Iftikhar SY, James PD, Steele RJC, Hardcastle JD, Atkinson M (1992) Length of Barrett’s oesophagus: an important factor in the development of dysplasia and adenocarcinoma. Gut 33:1155–1158

    PubMed  CAS  Google Scholar 

  37. Hirota WK, Loughney TM, Lazas DJ, Maydonovitch CL, Rholl V, Wong RKH (1999) Specialized intestinal metaplasia, dysplasia, and cancer of the esophagus and esophagogastric junction: Prevalence and clinical data. Gastroenterology 116:277–285

    Article  PubMed  CAS  Google Scholar 

  38. Riddell RH, Goldman H, Ransohoff DF, Appelman HD, Fenoglio CM, Haggitt RC, Ahren C, Correa P, Hamilton SR, Morson BC, Sommers SC, Yardley JH (1983) Dysplasia in inflammatory bowel disease: Standardized classification with provisional clinical applications. Hum Pathol 14:931–968

    Article  PubMed  CAS  Google Scholar 

  39. Reid BJ, Haggitt RC, Rubin CE, Roth G, Surawicz CM, Van Belle G, Lewin K, Weinstein WM, Antonioli DA, Goldman H, MacDonald W, Owen D (1988) Observer variation in the diagnosis of dysplasia in Barrett’s esophagus. Hum Pathol 19:166–178

    Article  PubMed  CAS  Google Scholar 

  40. Spechler SJ (1999) The role of gastric carditis in metaplasia and neoplasia at the gastroesophageal junction. Gastroenterology 117:218–228

    Article  PubMed  CAS  Google Scholar 

  41. Hayashi GM, Haggitt RC (2001) The histology of Barrett’s esophagus: Metaplasia and dysplasia. In: P Sharma, RE Sampliner (eds) Barrett’s esophagus and esophageal adenocarcinoma. Blackwell Science, London, pp. 80–88

    Google Scholar 

  42. Kerneis S, Pringault E (1999) Plasticity of the gastrointestinal epithelium: The M cell paradigm and opportunism of pathogenic microorganisms. Semin Immunol 11:205–215

    Article  PubMed  CAS  Google Scholar 

  43. Takubo K, Arai T, Sawabe M, Miyashita M, Sasajima K, Iwakiri K, Mafune K (2003) Structures of the normal esophagus and Barrett’s esophagus. Esophagus 1:37–47

    Article  Google Scholar 

  44. Takubo K (1981) Squamous metaplasia with reserve cell hyperplasia in the esophagogastric junction zone. Acta Pathol Jpn 31:349–359

    Google Scholar 

  45. Takubo K, Tsuchiya S, Fukushi K, Shirota A, Mitomo Y (1981) Dysplasia and reserve cell hyperplasia—like change in the human esophagus. Arch Pathol Jpn 31:999–1013

    Google Scholar 

  46. Su Y, Chen X, Klein M, Fang M, Wang S, Yang CS, Goyal RK (2004) Phenotype of columnar-lined esophagus in rats with esophagogastroduodenal anastomosis: similarity to human Barrett’s esophagus. Lab Invest 84:753–765

    Article  PubMed  Google Scholar 

  47. Fass R, Hell RW, Garewal HS, Martinez P, Pulliam G, Wendel C, Sampliner RE (2001) Correlation of oesophageal acid exposure with Barrett’s oesophagus length. Gut 48:310–313

    Article  PubMed  CAS  Google Scholar 

  48. Wong DJ, Paulson TG, Prevo LJ, Galipeau PC, Longton G, Blount PL, Reid BJ (2001) P16(INK4a) lesions are common, early abnormalities that undergo clonal expansion in Barrett’s metaplastic epithelium. Cancer Res 61:8284–8289

    PubMed  CAS  Google Scholar 

  49. Sampliner RE (2002) The Practice Parameters Committee of the American College of Gastroenterology. Updated guidelines for the diagnosis, surveillance and therapy of Barrett’s esophagus. Am J Gastroenterol 97:1888–1895

    Article  PubMed  Google Scholar 

  50. Dougherty TJ, Gomer CJ, Henderson BW, Jori G, Kessel D, Korbelik M, Moan J, Peng Q (1998) Photodynamic therapy. J Natl Cancer Inst 90:889–905

    Article  PubMed  CAS  Google Scholar 

  51. Wolfsen HC, Woodward TA, Raimondo M (2002) Photodynamic therapy for dysplastic Barrett’s esophagus and early esophageal adenocarcinoma. Mayo Clin Proc 77:1176–1181

    Article  PubMed  CAS  Google Scholar 

  52. Hur C, Nishioka NS, Gazelle GS (2003) Cost-effectiveness of photodynamic therapy for treatment of Barrett’s esophagus with high grade dysplasia. Dig Dis Sci 48:1273–1283

    Article  PubMed  Google Scholar 

  53. Overholt BF, Panjehpour M, Halberg DL (2003) Photodynamic therapy for Barrett’s esophagus with dysplasia and/or early stage carcinoma: Long term results. Gastrointest Endosc 58:183–188

    Article  PubMed  Google Scholar 

  54. Barr H (2001) The role of ablation in the management of high-grade dysplasia. In: HW Tilanus, SEA Attwood (eds) Barrett’s esophagus. Kluwer Academic Publishers, The Netherlands, pp. 259–272

    Google Scholar 

  55. Biddlestone LR, Barham CP, Wilkinson SP, Barr H, Shepherd NA (1998) The histopathology of treated Barrett’s esophagus: Squamous reepithelization after acid suppression and laser and photodynamic therapy. Am J Surg Pathol 22:239–245

    Article  PubMed  CAS  Google Scholar 

  56. Berenson MM, Johnson TD, Markowitz NR, Buchi KN, Samowitz WS (1993) Restoration of squamous mucosa after ablation of Barrett’s esophageal epithelium. Gastroenterology 104:1686–1691

    PubMed  CAS  Google Scholar 

  57. Wieczorek TJ, Wang HH, Antonioli DA, Glickman JN, Odze RD (2003) Pathologic features of reflux and Helicobacter pylori-associated carditis: A comparative study. Am J Surg Pathol 27:960–968

    Article  PubMed  Google Scholar 

  58. Glickman JN, Fox V, Antonioli DA, Wang HH, Odze RD (2002) Morphology of the cardia and significance of carditis in pediatric patients. Am J Surg Pathol 26:1032–1039

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Dr Melissa Upton was supported in part by the Beth Israel Pathology Foundation, Boston, Massachusetts. Dr Helen Shields was supported in part by the Leo and Natalie Wolf Cancer Research Fund and the Dr A. Stone Freedberg fund at the Beth Israel Deaconess Medical Center. This study was presented in part as an abstract at the American Gastroenterological Association’s Annual Meeting at Digestive Disease Week in May 2003 in Orlando, Florida. We are grateful to Dr Jerry Trier of Brigham and Women’s Hospital and Drs Harvey Goldman and Helen Wang of Beth Israel Deaconess Medical Center for their helpful suggestions and critical review of the manuscript. We are indebted to Jeanne Crowgey and Susan Rakich for their assistance with preparation of the manuscript. We greatly appreciate the technical assistance of Jane Hayward for the preparation of tables. We are indebted to Justine Curley and Daniel Brown of the Core Morphology group of the Harvard Digestive Disease Center for the preparation of the photomicrograph. Statistical analysis were performed and interpreted by Dr Bernard Ransil on the Prophet System (Release 4.1), a national computing resource for life science research sponsored by the NIH Division of Research Resources.

Author information

Authors and Affiliations

  1. Department of Pathology, University of Washington Medical Center and University of Washington Medical School, Seattle, Washington, USA

    Melissa P. Upton

  2. Departments of Pathology (MU), Neurology (BR), and Medicine (SR, HS), Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts, USA

    Melissa P. Upton, Bernard J. Ransil, Stanley J. Rosenberg & Helen M. Shields

  3. Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA

    Norman S. Nishioka & William P. Puricelli

  4. Department of Medicine, Greenwich Hospital, Greenwich, Connecticut and Yale Medical School, New Haven, Connecticut, USA

    Felice R. Zwas

  5. Beth Israel Deaconess Medical Center, Division of Gastroenterology, 330 Brookline Avenue, Boston, Massachusetts, 02215, USA

    Helen M. Shields

Authors
  1. Melissa P. Upton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Norman S. Nishioka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bernard J. Ransil
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stanley J. Rosenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. William P. Puricelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Felice R. Zwas
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Helen M. Shields
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Helen M. Shields.

Additional information

*Deceased.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Upton, M.P., Nishioka, N.S., Ransil, B.J. et al. Multilayered Epithelium May Be Found in Patients With Barrett’s Epithelium and Dysplasia or Adenocarcinoma. Dig Dis Sci 51, 1783–1790 (2006). https://doi.org/10.1007/s10620-006-9243-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-006-9243-9

Keywords

Search

Navigation