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Clinical Implications of Molecular Changes in Pediatric Barrett’s Esophagus

  • Pediatric Gastroenterology (SR Orenstein, Section Editor)
  • Published:
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Abstract

Barrett’s esophagus (BE) is a preneoplastic condition that predisposes to esophageal adenocarcinoma. Although data on the occurrence of BE in children are limited, recent studies have suggested an increase in the pediatric population. BE is thought to be a complex disease in which individual genetic predisposition interacts with environmental stimuli. Early premalignant clones produce biological and genetic heterogeneity, resulting in stepwise changes in differentiation, proliferation, and apoptosis, allowing disease progression under selective pressure. The value of endoscopic surveillance biopsy for dysplasia and carcinoma in patients with BE is controversial. Thus, the recognition of early and objective alternative risk markers, less susceptible of sampling error, will be of relevance in the management of BE patients. The possibility of performing molecular genetics on paraffin-embedded biopsies will expand our understanding of the natural history of BE and may lead to the use of biomarkers to inform treatment strategies.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. • Maltby EL, Dyson MJ, Wheeler MR, Thomson M, Sethuraman C, Cohen MC. Molecular abnormalities in pediatric barrett esophagus: can we test for potential of neoplastic progression? Pediatr Dev Pathol. 2010;13(4):310–7. This is the 1st evidence that the characteristic epithelial change in BE is associated with genetic changes in children as well as adults, inferring that relatively short periods of exposure to GERD can have this effect in some patients. The importance of this study is that even at the pediatric level, BE can show genetic changes associated with neoplastic progression.

  2. Sharma P, McQuaid K, Dent J, Fennerty MB, Sampliner R, Spechler S, et al. A critical review of the diagnosis and management of Barrett’s esophagus: the AGA Chicago Workshop. Gastroenterology. 2004;127(1):310–30.

    Article  PubMed  Google Scholar 

  3. Hassall E. Barrett’s esophagus: new definitions and approaches in children. J Pediatr Gastroenterol Nutr. 1993;16(4):345–64.

    Article  PubMed  CAS  Google Scholar 

  4. Hassall E. Barrett’s esophagus: congenital or acquired? Am J Gastroenterol. 1993;88(6):819–24.

    PubMed  CAS  Google Scholar 

  5. Weinstein WM, Ippoliti AF. The diagnosis of Barrett’s esophagus: goblets, goblets, goblets. Gastrointest Endosc. 1996;44(1):91–5.

    Article  PubMed  CAS  Google Scholar 

  6. • Jeurnink SM, van Herwaarden-Lindeboom MY, Siersema PD, Fischer K, Houwen RH, van der Zee DC. Barrett’s esophagus in children: does it need more attention? Dig Liver Dis. 2011;43(9):682–7. This review summarizes published results on the presence of BE in pediatric patients with GERD and shows that BE may develop in children with reflux symptoms after a mean period of 5.3 years. In addition, BE may also result in the development of esophageal adenocarcinoma, demonstrating that this phenomenon may also occur in the pediatric population.

  7. Orenstein SR, Izadnia F, Khan S. Gastroesophageal reflux disease in children. Gastroenterol Clin North Am. 1999;28(4):947–69.

    Article  PubMed  CAS  Google Scholar 

  8. Cohen MC, Vergani P, Vigovich F, Thomson M, Taylor CJ, Hammond D. Investigation of genomic instability in paediatric Barrett’s oesophagus using laser microdissection on paraffin-embedded endoscopic biopsies. J Pediatr Gastroenterol Nutr. 2007;45(1):44–9.

    Article  PubMed  Google Scholar 

  9. • Jin Z, Cheng Y, Gu W, Zheng Y, Sato F, Mori Y, et al. A multicenter, double-blinded validation study of methylation biomarkers for progression prediction in Barrett’s esophagus. Cancer Res. 2009;69(10):4112–5. These findings indicate that although performing at high specificity, these biomarker models predicted half of progressors to HGD and EAC that would not have been diagnosed earlier without using these biomarkers.

    Article  PubMed  CAS  Google Scholar 

  10. El-Serag HB, Gilger MA, Shub MD, Richardson P, Bancroft J. The prevalence of suspected Barrett’s esophagus in children and adolescents: a multicenter endoscopic study. Gastrointest Endosc. 2006;64(5):671–5.

    Article  PubMed  Google Scholar 

  11. Gold BD. Outcomes of pediatric gastroesophageal reflux disease: in the first year of life, in childhood, and in adults…oh, and should we really leave Helicobacter pylori alone? J Pediatr Gastroenterol Nutr. 2003;37 Suppl 1:S33–9.

    PubMed  Google Scholar 

  12. Peuchmaur M, Potet F, Goldfain D. Mucin histochemistry of the columnar epithelium of the oesophagus (Barrett’s oesophagus): a prospective biopsy study. J Clin Pathol. 1984;37(6):607–10.

    Article  PubMed  CAS  Google Scholar 

  13. Cohen MC, Ashok D, Gell M, Bishop J, Walker J, Thomson M, et al. Pediatric columnar lined esophagus vs Barrett’s esophagus: is it the time for a consensus definition. Pediatr Dev Pathol. 2009;12(2):116–26.

    Article  PubMed  Google Scholar 

  14. Dahms BBQS. Gastrointestinal Diseases. Perspect Pediatr Pathol. 1997;20:35–76.

    Article  Google Scholar 

  15. Paull A, Trier JS, Dalton MD, Camp RC, Loeb P, Goyal RK. The histologic spectrum of Barrett’s esophagus. N Engl J Med. 1976;295(9):476–80.

    Article  PubMed  CAS  Google Scholar 

  16. Oberg S, Johansson J, Wenner J, Johnsson F, Zilling T, von Holstein CS, et al. Endoscopic surveillance of columnar-lined esophagus: frequency of intestinal metaplasia detection and impact of antireflux surgery. Ann Surg. 2001;234(5):619–26.

    Article  PubMed  CAS  Google Scholar 

  17. DeMeester SR, DeMeester TR. Columnar mucosa and intestinal metaplasia of the esophagus: fifty years of controversy. Ann Surg. 2000;231(3):303–21.

    Article  PubMed  CAS  Google Scholar 

  18. Gastroenterology BSo. Guidelines for the diagnosis and management of Barrett’s columnar-lined oesophagus. 2005; http://www.bsg.org.uk.

  19. van Blankenstein M, Looman CW, Johnston BJ, Caygill CP. Age and sex distribution of the prevalence of Barrett’s esophagus found in a primary referral endoscopy center. Am J Gastroenterol. 2005;100(3):568–76.

    Article  PubMed  Google Scholar 

  20. Wang KK, Sampliner RE. Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett’s esophagus. Am J Gastroenterol. 2008;103(3):788–97.

    Article  PubMed  Google Scholar 

  21. Sherman PM, Hassall E, Fagundes-Neto U, Gold BD, Kato S, Koletzko S, et al. A global, evidence-based consensus on the definition of gastroesophageal reflux disease in the pediatric population. Am J Gastroenterol. 2009;104(5):1278–95. quiz 96.

    Article  PubMed  Google Scholar 

  22. Qualman SJ, Murray RD, McClung HJ, Lucas J. Intestinal metaplasia is age related in Barrett’s esophagus. Arch Pathol Lab Med. 1990;114(12):1236–40.

    PubMed  CAS  Google Scholar 

  23. Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101(8):1900–20. quiz 43.

    Article  PubMed  Google Scholar 

  24. Spechler SJ, Goyal RK. The columnar-lined esophagus, intestinal metaplasia, and Norman Barrett. Gastroenterology. 1996;110(2):614–21.

    Article  PubMed  CAS  Google Scholar 

  25. Hassall E. Cardia-type mucosa as an esophageal metaplastic condition in children: “Barrett esophagus, intestinal metaplasia-negative?”. [corrected]. J Pediatr Gastroenterol Nutr. 2008;47(1):102–6.

    Article  PubMed  Google Scholar 

  26. Sampliner RE. Practice guidelines on the diagnosis, surveillance, and therapy of Barrett’s esophagus. The Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol. 1998;93(7):1028–32.

    Article  PubMed  CAS  Google Scholar 

  27. Sarbia M, Donner A, Franke C, Gabbert HE. Distinction between intestinal metaplasia in the cardia and in Barrett’s esophagus: the role of histology and immunohistochemistry. Hum Pathol. 2004;35(3):371–6.

    Article  PubMed  Google Scholar 

  28. DeNardi FG RR. Esohagus. In: Histology for pathologist, 3 rd edition. Sternberg SS Lippincott Williams & Wilkins Philadelphia 2007:565–88.

  29. Sampliner RE. Updated guidelines for the diagnosis, surveillance, and therapy of Barrett’s esophagus. Am J Gastroenterol. 2002;97(8):1888–95.

    Article  PubMed  Google Scholar 

  30. Beck F, Chawengsaksophak K, Waring P, Playford RJ, Furness JB. Reprogramming of intestinal differentiation and intercalary regeneration in Cdx2 mutant mice. Proc Natl Acad Sci U S A. 1999;96(13):7318–23.

    Article  PubMed  CAS  Google Scholar 

  31. Moskaluk CA, Zhang H, Powell SM, Cerilli LA, Hampton GM, Frierson Jr HF. Cdx2 protein expression in normal and malignant human tissues: an immunohistochemical survey using tissue microarrays. Mod Pathol. 2003;16(9):913–9.

    Article  PubMed  Google Scholar 

  32. Phillips RW, Frierson Jr HF, Moskaluk CA. Cdx2 as a marker of epithelial intestinal differentiation in the esophagus. Am J Surg Pathol. 2003;27(11):1442–7.

    Article  PubMed  Google Scholar 

  33. Moons LMGBD, Kuipers EJ, et al. The homeodomain protein CDX2 is an early marker of Barrett’s oesophagus. J Clin Pathol. 2005;9:218–27.

    Google Scholar 

  34. Weinstein W. Erosive esophagitis impairs accurate detection of Barrett’s esophagus: a prospective randomized double blind study. Gastroenterology 1999;116: A352 (G1538).

  35. Schmitz RJSP, Topaloski M. Detection of Barrett’s esophagus after endoscopic healing for erosive esophagitis. Am J Gastroenterol. 2000;95:2433.

    Article  Google Scholar 

  36. El-Serag HB, Aguirre TV, Davis S, Kuebeler M, Bhattacharyya A, Sampliner RE. Proton pump inhibitors are associated with reduced incidence of dysplasia in Barrett’s esophagus. Am J Gastroenterol. 2004;99(10):1877–83.

    Article  PubMed  CAS  Google Scholar 

  37. Hillman LC, Chiragakis L, Shadbolt B, Kaye GL, Clarke AC. Proton-pump inhibitor therapy and the development of dysplasia in patients with Barrett’s oesophagus. Med J Aust. 2004;180(8):387–91.

    PubMed  Google Scholar 

  38. Ouatu-Lascar R, Fitzgerald RC, Triadafilopoulos G. Differentiation and proliferation in Barrett’s esophagus and the effects of acid suppression. Gastroenterology. 1999;117(2):327–35.

    Article  PubMed  CAS  Google Scholar 

  39. Hofstetter WL, Peters JH, DeMeester TR, Hagen JA, DeMeester SR, Crookes PF, et al. Long-term outcome of antireflux surgery in patients with Barrett’s esophagus. Ann Surg. 2001;234(4):532–8. discussion 8–9.

    Article  PubMed  CAS  Google Scholar 

  40. Csendes A, Burdiles P, Braghetto I, Korn O. Adenocarcinoma appearing very late after antireflux surgery for Barrett’s esophagus: long-term follow-up, review of the literature, and addition of six patients. J Gastrointest Surg. 2004;8(4):434–41.

    Article  PubMed  Google Scholar 

  41. Bani-Hani KE, Bani-Hani BK, Martin IG. Characteristics of patients with columnar-lined Barrett’s esophagus and risk factors for progression to esophageal adenocarcinoma. World J Gastroenterol. 2005;11(43):6807–14.

    PubMed  Google Scholar 

  42. Macdonald CE, Wicks AC, Playford RJ. Ten years’ experience of screening patients with Barrett’s oesophagus in a university teaching hospital. Gut. 1997;41(3):303–7.

    Article  PubMed  CAS  Google Scholar 

  43. Robertson CS, Mayberry JF, Nicholson DA, James PD, Atkinson M. Value of endoscopic surveillance in the detection of neoplastic change in Barrett’s oesophagus. Br J Surg. 1988;75(8):760–3.

    Article  PubMed  CAS  Google Scholar 

  44. Achkar E, Carey W. The cost of surveillance for adenocarcinoma complicating Barrett’s esophagus. Am J Gastroenterol. 1988;83(3):291–4.

    PubMed  CAS  Google Scholar 

  45. Sikkema M, de Jonge PJ, Steyerberg EW, Kuipers EJ. Risk of esophageal adenocarcinoma and mortality in patients with Barrett’s esophagus: a systematic review and meta-analysis. Clin Gastroenterol Hepatol;8(3):235–44; quiz e32.

  46. Armstrong D, Marshall JK, Chiba N, Enns R, Fallone CA, Fass R, et al. Canadian Consensus Conference on the management of gastroesophageal reflux disease in adults - update 2004. Can J Gastroenterol. 2005;19(1):15–35.

    PubMed  Google Scholar 

  47. Barbiere JM, Lyratzopoulos G. Cost-effectiveness of endoscopic screening followed by surveillance for Barrett’s esophagus: a review. Gastroenterology. 2009;137(6):1869–76.

    Article  PubMed  Google Scholar 

  48. Crockett SD, Lipkus IM, Bright SD, Sampliner RE, Wang KK, Boolchand V, et al. Overutilization of endoscopic surveillance in nondysplastic Barrett’s esophagus: a multicenter study. Gastrointest Endosc 2011.

  49. Wani S, Mathur S, Sharma P. How to manage a Barrett’s esophagus patient with low-grade dysplasia. Clin Gastroenterol Hepatol. 2009;7(1):27–32.

    Article  PubMed  Google Scholar 

  50. Wani S, Falk GW, Post J, Yerian L, Hall M, Wang A, et al. Risk factors for progression of low-grade dysplasia in patients with Barrett’s esophagus. Gastroenterology. 2011;141(4):1179–86. 86 e1.

    Article  PubMed  Google Scholar 

  51. Streitz Jr JM, Andrews Jr CW, Ellis Jr FH. Endoscopic surveillance of Barrett’s esophagus. Does it help? J Thorac Cardiovasc Surg. 1993;105(3):383–7. discussion 7–8.

    PubMed  Google Scholar 

  52. Corley DA, Levin TR, Habel LA, Weiss NS, Buffler PA. Surveillance and survival in Barrett’s adenocarcinomas: a population-based study. Gastroenterology. 2002;122(3):633–40.

    Article  PubMed  Google Scholar 

  53. Montgomery E, Bronner MP, Goldblum JR, Greenson JK, Haber MM, Hart J, et al. Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation. Hum Pathol. 2001;32(4):368–78.

    Article  PubMed  CAS  Google Scholar 

  54. Montgomery E, Goldblum JR, Greenson JK, Haber MM, Lamps LW, Lauwers GY, et al. Dysplasia as a predictive marker for invasive carcinoma in Barrett esophagus: a follow-up study based on 138 cases from a diagnostic variability study. Hum Pathol. 2001;32(4):379–88.

    Article  PubMed  CAS  Google Scholar 

  55. Alikhan M, Rex D, Khan A, Rahmani E, Cummings O, Ulbright TM. Variable pathologic interpretation of columnar lined esophagus by general pathologists in community practice. Gastrointest Endosc. 1999;50(1):23–6.

    Article  PubMed  CAS  Google Scholar 

  56. Rogers EL, Goldkind SF, Iseri OA, Bustin M, Goldkind L, Hamilton SR, et al. Adenocarcinoma of the lower esophagus. A disease primarily of white men with Barrett’s esophagus. J Clin Gastroenterol. 1986;8(6):613–8.

    Article  PubMed  CAS  Google Scholar 

  57. Gopal DV, Lieberman DA, Magaret N, Fennerty MB, Sampliner RE, Garewal HS, et al. Risk factors for dysplasia in patients with Barrett’s esophagus (BE): results from a multicenter consortium. Dig Dis Sci. 2003;48(8):1537–41.

    Article  PubMed  Google Scholar 

  58. Wright TA, Gray MR, Morris AI, Gilmore IT, Ellis A, Smart HL, et al. Cost effectiveness of detecting Barrett’s cancer. Gut. 1996;39(4):574–9.

    Article  PubMed  CAS  Google Scholar 

  59. Menke-Pluymers MB, Hop WC, Dees J, van Blankenstein M, Tilanus HW. Risk factors for the development of an adenocarcinoma in columnar-lined (Barrett) esophagus. The Rotterdam Esophageal Tumor Study Group. Cancer. 1993;72(4):1155–8.

    Article  PubMed  CAS  Google Scholar 

  60. Schnell TG, Sontag SJ, Chejfec G. Adenocarcinomas arising in tongues or short segments of Barrett’s esophagus. Dig Dis Sci. 1992;37(1):137–43.

    Article  PubMed  CAS  Google Scholar 

  61. Cameron AJ, Lomboy CT, Pera M, Carpenter HA. Adenocarcinoma of the esophagogastric junction and Barrett’s esophagus. Gastroenterology. 1995;109(5):1541–6.

    Article  PubMed  CAS  Google Scholar 

  62. Iftikhar SY, James PD, Steele RJ, Hardcastle JD, Atkinson M. Length of Barrett’s oesophagus: an important factor in the development of dysplasia and adenocarcinoma. Gut. 1992;33(9):1155–8.

    Article  PubMed  CAS  Google Scholar 

  63. Avidan B, Sonnenberg A, Schnell TG, Chejfec G, Metz A, Sontag SJ. Hiatal hernia size, Barrett’s length, and severity of acid reflux are all risk factors for esophageal adenocarcinoma. Am J Gastroenterol. 2002;97(8):1930–6.

    Article  PubMed  Google Scholar 

  64. Weston AP, Badr AS, Hassanein RS. Prospective multivariate analysis of clinical, endoscopic, and histological factors predictive of the development of Barrett’s multifocal high-grade dysplasia or adenocarcinoma. Am J Gastroenterol. 1999;94(12):3413–9.

    Article  PubMed  CAS  Google Scholar 

  65. Rudolph RE, Vaughan TL, Storer BE, Haggitt RC, Rabinovitch PS, Levine DS, et al. Effect of segment length on risk for neoplastic progression in patients with Barrett esophagus. Ann Intern Med. 2000;132(8):612–20.

    PubMed  CAS  Google Scholar 

  66. Van der Veen AH, Dees J, Blankensteijn JD, Van Blankenstein M. Adenocarcinoma in Barrett’s oesophagus: an overrated risk. Gut. 1989;30(1):14–8.

    Article  PubMed  Google Scholar 

  67. Moghissi K, Sharpe DA, Pender D. Adenocarcinoma and Barrett’s oesophagus. A clinico-pathological study. Eur J Cardiothorac Surg. 1993;7(3):126–31.

    Article  PubMed  CAS  Google Scholar 

  68. Lerut T, Coosemans W, Van Raemdonck D, Dillemans B, De Leyn P, Marnette JM, et al. Surgical treatment of Barrett’s carcinoma. Correlations between morphologic findings and prognosis. J Thorac Cardiovasc Surg. 1994;107(4):1059–65. discussion 65–6.

    PubMed  CAS  Google Scholar 

  69. Lagergren J, Bergstrom R, Lindgren A, Nyren O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med. 1999;340(11):825–31.

    Article  PubMed  CAS  Google Scholar 

  70. Brown LM, Swanson CA, Gridley G, Swanson GM, Schoenberg JB, Greenberg RS, et al. Adenocarcinoma of the esophagus: role of obesity and diet. J Natl Cancer Inst. 1995;87(2):104–9.

    Article  PubMed  CAS  Google Scholar 

  71. Lagergren J, Bergstrom R, Nyren O. Association between body mass and adenocarcinoma of the esophagus and gastric cardia. Ann Intern Med. 1999;130(11):883–90.

    PubMed  CAS  Google Scholar 

  72. Skinner DB, Walther BC, Riddell RH, Schmidt H, Iascone C, DeMeester TR. Barrett’s esophagus. Comparison of benign and malignant cases. Ann Surg. 1983;198(4):554–65.

    Article  PubMed  CAS  Google Scholar 

  73. Gray MR, Donnelly RJ, Kingsnorth AN. The role of smoking and alcohol in metaplasia and cancer risk in Barrett’s columnar lined oesophagus. Gut. 1993;34(6):727–31.

    Article  PubMed  CAS  Google Scholar 

  74. Bani-Hani K, Martin IG, Hardie LJ, Mapstone N, Briggs JA, Forman D, et al. Prospective study of cyclin D1 overexpression in Barrett’s esophagus: association with increased risk of adenocarcinoma. J Natl Cancer Inst. 2000;92(16):1316–21.

    Article  PubMed  CAS  Google Scholar 

  75. Wild CP, Forman D. Surveillance for Barrett’s oesophagus. It is too early to dismiss surveillance programmes. Bmj. 2001;322(7294):1125. author reply 6.

    PubMed  CAS  Google Scholar 

  76. Coad RASN. Barrett’s oesophagus: definition, diagnosis and patholgenesis. Curr Diag Pathol. 2003;9:218–27.

    Article  Google Scholar 

  77. Barrett MT, Galipeau PC, Sanchez CA, Emond MJ, Reid BJ. Determination of the frequency of loss of heterozygosity in esophageal adenocarcinoma by cell sorting, whole genome amplification and microsatellite polymorphisms. Oncogene. 1996;12(9):1873–8.

    PubMed  CAS  Google Scholar 

  78. Gleeson CM, Sloan JM, McGuigan JA, Ritchie AJ, Weber JL, Russell SE. Barrett’s oesophagus: microsatellite analysis provides evidence to support the proposed metaplasia-dysplasia-carcinoma sequence. Genes Chromosomes Cancer. 1998;21(1):49–60.

    Article  PubMed  CAS  Google Scholar 

  79. Moskaluk CA, Hu J, Perlman EJ. Comparative genomic hybridization of esophageal and gastroesophageal adenocarcinomas shows consensus areas of DNA gain and loss. Genes Chromosomes Cancer. 1998;22(4):305–11.

    Article  PubMed  CAS  Google Scholar 

  80. van Dekken H, Geelen E, Dinjens WN, Wijnhoven BP, Tilanus HW, Tanke HJ, et al. Comparative genomic hybridization of cancer of the gastroesophageal junction: deletion of 14Q31-32.1 discriminates between esophageal (Barrett’s) and gastric cardia adenocarcinomas. Cancer Res. 1999;59(3):748–52.

    PubMed  Google Scholar 

  81. Sanz-Ortega J, Hernandez S, Saez MC, Sierra E, Sanz-Ortega G, Torres A, et al. 3p21, 5q21, 9p21 and 17p13.1 allelic deletions are potential markers of individuals with a high risk of developing adenocarcinoma in Barrett’s epithelium without dysplasia. Hepatogastroenterology. 2003;50(50):404–7.

    PubMed  CAS  Google Scholar 

  82. Rabinovitch PS, Reid BJ, Haggitt RC, Norwood TH, Rubin CE. Progression to cancer in Barrett’s esophagus is associated with genomic instability. Lab Invest. 1989;60(1):65–71.

    PubMed  CAS  Google Scholar 

  83. Evans SC, Gillis A, Geldenhuys L, Vaninetti NM, Malatjalian DA, Porter GA, et al. Microsatellite instability in esophageal adenocarcinoma. Cancer Lett. 2004;212(2):241–51.

    Article  PubMed  CAS  Google Scholar 

  84. Suraweera N, Duval A, Reperant M, Vaury C, Furlan D, Leroy K, et al. Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR. Gastroenterology. 2002;123(6):1804–11.

    Article  PubMed  CAS  Google Scholar 

  85. Jankowski JA, Wright NA, Meltzer SJ, Triadafilopoulos G, Geboes K, Casson AG, et al. Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. Am J Pathol. 1999;154(4):965–73.

    Article  PubMed  CAS  Google Scholar 

  86. Wang S, Zhan M, Yin J, Abraham JM, Mori Y, Sato F, et al. Transcriptional profiling suggests that Barrett’s metaplasia is an early intermediate stage in esophageal adenocarcinogenesis. Oncogene. 2006;25(23):3346–56.

    Article  PubMed  CAS  Google Scholar 

  87. Fahmy M, Skacel M, Gramlich TL, Brainard JA, Rice TW, Goldblum JR, et al. Chromosomal gains and genomic loss of p53 and p16 genes in Barrett’s esophagus detected by fluorescence in situ hybridization of cytology specimens. Mod Pathol. 2004;17(5):588–96.

    Article  PubMed  CAS  Google Scholar 

  88. Cohen MME. Recent developments in understanding paediatric Barrett’s oesophagus: A review. Open Pathology Journal. 2010;4:60–6.

    Google Scholar 

  89. Barrett MT, Sanchez CA, Galipeau PC, Neshat K, Emond M, Reid BJ. Allelic loss of 9p21 and mutation of the CDKN2/p16 gene develop as early lesions during neoplastic progression in Barrett’s esophagus. Oncogene. 1996;13(9):1867–73.

    PubMed  CAS  Google Scholar 

  90. Wong DJ, Paulson TG, Prevo LJ, Galipeau PC, Longton G, Blount PL, et al. p16(INK4a) lesions are common, early abnormalities that undergo clonal expansion in Barrett’s metaplastic epithelium. Cancer Res. 2001;61(22):8284–9.

    PubMed  CAS  Google Scholar 

  91. Rossi E, Grisanti S, Villanacci V, Della Casa D, Cengia P, Missale G, et al. HER-2 overexpression/amplification in Barrett’s oesophagus predicts early transition from dysplasia to adenocarcinoma: a clinico-pathologic study. J Cell Mol Med. 2009;13(9B):3826–33.

    Article  PubMed  Google Scholar 

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  1. Department of Paediatrics, Pugliese-Ciaccio Hospital, University “Magna Græcia” of Catanzaro, Viale Pio X, 88100, Catanzaro, Italy

    Licia Pensabene

  2. Department of Histopathology, Sheffield Children’s NHS Foundation Trust, Western Bank, Sheffield, S10 2TH, UK

    Marta C. Cohen

  3. Department of Paediatrics, Sheffield Children’s NHS Foundation Trust, Western Bank, Sheffield, S10 2TH, UK

    Michael Thomson

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  1. Licia Pensabene
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Pensabene, L., Cohen, M.C. & Thomson, M. Clinical Implications of Molecular Changes in Pediatric Barrett’s Esophagus. Curr Gastroenterol Rep 14, 253–261 (2012). https://doi.org/10.1007/s11894-012-0252-x

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