Skip to main content

The Pathogenesis of Barrett’s Metaplasia and the Progression to Esophageal Adenocarcinoma

  • Chapter
  • First Online:
Adenocarcinoma of the Esophagogastric Junction

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 182))

Abstract

The most important risk factor for the development of Barrett’s esophagus is the reflux of both gastric and duodenal contents into the esophagus. The reason why Barrett’s metaplasia develops only in a minority of patients suffering from gastroesophageal reflux disease remains unknown.The exact mechanism behind the transition of normal squamous epithelium into specialized columnar epithelium is also unclear. It is likely that stem cells are involved in this metaplastic change, as they are the only permanent residents of the epithelium. Several tumorigenic steps that lead to the underlying genetic instability, which is indispensable in the progression from columnar metaplasia to esophageal adenocarcinoma have been des­c­rib­ed. This review outlines the process of pathogenesis of Barrett’s metaplasia and its pro­gression to esophageal adenocarcinoma.

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

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abdel-Latif MM, O’Riordan JM, Ravi N, Kelleher D, Reynolds JV (2005) Activated nuclear factor-kappa B and cytokine profiles in the esophagus parallel tumor regression following neoadjuvant chemoradiotherapy. Dis Esophagus 18:246–252

    PubMed  CAS  Google Scholar 

  • al-Kasspooles M, Moore JH, Orringer MB, Beer DG (1993) Amplification and over-expression of the EGFR and erbB-2 genes in human esophageal adenocarcinomas. Int J Cancer 54:213–219

    Google Scholar 

  • Allison PR, Johnstone AS (1953) The oesophagus lined with gastric mucous membrane. Thorax 8:87–101

    PubMed  CAS  Google Scholar 

  • Arber N, Lightdale C, Rotterdam H, Han KH, Sgambato A, Yap E, Ahsan H, Finegold J, Stevens PD, Green PH, Hibshoosh H, Neugut AI, Holt PR, Weinstein IB (1996) Increased expression of the cyclin D1 gene in Barrett’s esophagus. Cancer Epidemiol Biomarkers Prev 5:457–459

    PubMed  CAS  Google Scholar 

  • Aste H, Bonelli L, Ferraris R, Conio M, Lapertosa G (1999) Gastroesophageal reflux disease: relationship between clinical and histological features. GOSPE. Gruppo Operativo per lo Studio delle Precancerosi dell’Esofago. Dig Dis Sci 44:2412–2418

    PubMed  CAS  Google Scholar 

  • Atherfold PA, Jankowski JA (2006) Molecular bio­logy of Barrett’s cancer. Best Pract Res Clin Gastroenterol 20:813–827

    PubMed  CAS  Google Scholar 

  • Auvinen MI, Sihvo EI, Ruohtula T, Salminen JT, Koivistoinen A, Siivola P, Ronnholm R, Ramo JO, Bergman M, Salo JA (2002) Incipient angiogenesis in Barrett’s epithelium and lymphangiogenesis in Barrett’s adenocarcinoma. J Clin Oncol 20:2971–2979

    PubMed  Google Scholar 

  • Bahmanyar S, Zendehdel K, Nyren O, Ye W (2007) Risk of oesophageal cancer by histology among patients hospitalised for gastroduodenal ulcers. Gut 56:464–468

    PubMed  Google Scholar 

  • Bailey T, Biddlestone L, Shepherd N, Barr H, Warner P, Jankowski J (1998) Altered cadherin and catenin complexes in the Barrett’s eso­phagus-dysplasia-adenocarcinoma sequence: cor­relation with disease progression and de­diff­erentiation. Am J Pathol 152:135–144

    PubMed  CAS  Google Scholar 

  • Bani-Hani K, Martin IG, Hardie LJ, Mapstone N, Briggs JA, Forman D, Wild CP (2000) Pros­pective study of cyclin D1 overexpression in Barrett’s esophagus: association with increased risk of adenocarcinoma. J Natl Cancer Inst 92:1316–1321

    PubMed  CAS  Google Scholar 

  • Barnes PJ, Karin M (1997) Nuclear factor-kappa B: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 336:1066–1071

    PubMed  CAS  Google Scholar 

  • Barrett NR (1950) Chronic peptic ulcer of the oesophagus and ‘oesophagitis’. Br J Surg 38:175–182

    PubMed  CAS  Google Scholar 

  • Bjerkvig R, Tysnes BB, Aboody KS, Najbauer J, Terzis AJ (2005) Opinion: the origin of the cancer stem cell: current controversies and new insights. Nat Rev Cancer 5:899–904

    PubMed  CAS  Google Scholar 

  • Blot WJ, Devesa SS, Kneller RW, Fraumeni JF Jr (1991) Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 265:1287–1289

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Boynton RF, Blount PL, Yin J, Brown VL, Huang Y, Tong Y, McDaniel T, Newkirk C, Resau JH, Raskind WH et al (1992) Loss of heterozygosity involving the APC and MCC genetic loci occurs in the majority of human esophageal cancers. Proc Natl Acad Sci USA 89:3385–3388

    PubMed  CAS  Google Scholar 

  • Bremner CG, Lynch VP, Ellis FH 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 

  • Buskens CJ, Van Rees BP, Sivula A, Reitsma JB, Haglund C, Bosma PJ, Offerhaus GJ, Van Lanschot JJ, Ristimaki A (2002) Prognostic significance of elevated cyclooxygenase 2 expression in patients with adenocarcinoma of the esophagus. Gastroenterology 122:1800–1807

    PubMed  CAS  Google Scholar 

  • Buskens CJ, Ristimaki A, Offerhaus GJ, Richel DJ, van Lanschot JJ (2003) Role of cyclo­oxygenase-2 in the development and treatment of oesophageal adenocarcinoma. Scand J Gastroenterol Suppl: 87–93

    Google Scholar 

  • Buttar NS, Falk GW (2001) Pathogenesis of gastroesophageal reflux and Barrett esophagus. Mayo Clin Proc 76:226–234

    PubMed  CAS  Google Scholar 

  • Buttar NS, Wang KK (2004) Mechanisms of disease: carcinogenesis in Barrett’s esophagus. Nat Clin Pract Gastroenterol Hepatol 1:106–112

    PubMed  Google Scholar 

  • Buttar NS, Wang KK, Anderson MA, Dierkhising RA, Pacifico RJ, Krishnadath KK, Lutzke LS (2002) The effect of selective cyclooxygenase-2 inhibition in Barrett’s esophagus epithelium: an in vitro study. J Natl Cancer Inst 94:422–429

    PubMed  CAS  Google Scholar 

  • Caldwell MT, Lawlor P, Byrne PJ, Walsh TN, Hennessy TP (1995) Ambulatory oesophageal bile reflux monitoring in Barrett’s oesophagus. Br J Surg 82:657–660

    PubMed  CAS  Google Scholar 

  • Cameron AJ, Lomboy CT (1992) Barrett’s esophagus: age, prevalence, and extent of columnar epithelium. Gastroenterology 103:1241–1245

    PubMed  CAS  Google Scholar 

  • Cameron AJ, Ott BJ, Payne WS (1985) The incidence of adenocarcinoma in columnar-lined (Barrett’s) esophagus. N Engl J Med 313:857–859

    PubMed  CAS  Google Scholar 

  • Carney CN, Orlando RC, Powell DW, Dotson MM (1981) Morphologic alterations in early acid-induced epithelial injury of the rabbit esophagus. Lab Invest 45:198–208

    PubMed  CAS  Google Scholar 

  • Casson AG, Evans SC, Gillis A, Porter GA, Veugelers P, Darnton SJ, Guernsey DL, Hainaut P (2003) Clinical implications of p53 tumor suppressor gene mutation and protein expression in esophageal adenocarcinomas: results of a ten-year prospective study. J Thorac Cardiovasc Surg 125:1121–1131

    PubMed  CAS  Google Scholar 

  • Champion G, Richter JE, Vaezi MF, Singh S, Alexander R (1994) Duodenogastroesophageal reflux: relationship to pH and importance in Barrett’s esophagus. Gastroenterology 107:747–754

    PubMed  CAS  Google Scholar 

  • Chandrasoma PT, DeMeester TR (2006) Does columnar-lined esophagus increase in length? Does Barrett esophagus increase in length? In: GERD: Reflux to esophageal adenocarcinoma. Elsevier, Oxford, pp 190–192

    Google Scholar 

  • Chandrasoma PT, Der R, Ma Y, Peters J, Demeester T (2003) Histologic classification of patients based on mapping biopsies of the gastroesophageal junction. Am J Surg Pathol 27:929–936

    PubMed  Google Scholar 

  • Chang CL, Lao-Sirieix P, Save V, De La Cueva MG, Laskey R, Fitzgerald RC (2007) Retinoic acid-induced glandular differentiation of the oesophagus. Gut 56:906–917

    PubMed  CAS  Google Scholar 

  • Chow WH, Blaser MJ, Blot WJ, Gammon MD, Vaughan TL, Risch HA, Perez-Perez GI, ­Sch­oenberg JB, Stanford JL, Rotterdam H, West AB, Fraumeni JF Jr (1998) An inverse relation between cagA+ strains of Helicobacter pylori infection and risk of esophageal and gastric ­cardia adenocarcinoma. Cancer Res 58:588–590

    PubMed  CAS  Google Scholar 

  • Christofori G, Semb H (1999) The role of the ­cell-adhesion molecule E-cadherin as a tumour-suppressor gene. Trends Biochem Sci 24:73–76

    PubMed  CAS  Google Scholar 

  • Conio M, Filiberti R, Blanchi S, Ferraris R, Marchi S, Ravelli P, Lapertosa G, Iaquinto G, Sablich R, Gusmaroli R, Aste H, Giacosa A (2002) Risk factors for Barrett’s esophagus: a case-control study. Int J Cancer 97:225–229

    PubMed  CAS  Google Scholar 

  • Cook MB, Greenwood DC, Hardie LJ, Wild CP, Forman D (2008) A systematic review and meta-analysis of the risk of increasing adiposity on Barrett’s esophagus. Am J Gastroenterol 103:292–300

    PubMed  Google Scholar 

  • Cotsarelis G, Sun TT, Lavker RM (1990) Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell 61:1329–1337

    PubMed  CAS  Google Scholar 

  • Couvelard A, Paraf F, Gratio V, Scoazec JY, Henin D, Degott C, Flejou JF (2000) Angiogenesis in the neoplastic sequence of Barrett’s oesophagus. Correlation with VEGF expression. J Pathol 192:14–18

    PubMed  CAS  Google Scholar 

  • Csendes A, Maluenda F, Braghetto I, Csendes P, Henriquez A, Quesada MS (1993) Location of the lower oesophageal sphincter and the squamous columnar mucosal junction in 109 healthy controls and 778 patients with different degrees of endoscopic oesophagitis. Gut 34:21–27

    PubMed  CAS  Google Scholar 

  • De Lange T (2005) Telomere-related genome instability in cancer. Cold Spring Harb Symp Quant Biol 70:197–204

    PubMed  Google Scholar 

  • DeMeester TR (2001) Clinical biology of the Barrett’s metaplasia, dysplasia to carcinoma sequence. Surg Oncol 10:91–102

    PubMed  CAS  Google Scholar 

  • DeMeester SR, DeMeester TR (2000) Columnar mucosa and intestinal metaplasia of the eso­phagus: fifty years of controversy. Ann Surg 231:303–321

    PubMed  CAS  Google Scholar 

  • Devesa SS, Blot WJ, Fraumeni JF Jr (1998) Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer 83:2049–2053

    PubMed  CAS  Google Scholar 

  • Dixon MF, Neville PM, Mapstone NP, Moayyedi P, Axon AT (2001) Bile reflux gastritis and Barrett’s oesophagus: further evidence of a role for ­duodenogastro-oesophageal reflux? Gut 49:359–363

    PubMed  CAS  Google Scholar 

  • Drovdlic CM, Goddard KA, Chak A, Brock W, Chessler L, King JF, Richter J, Falk GW, Johnston DK, Fisher JL, Grady WM, Lemeshow S, Eng C (2003) Demographic and phenotypic features of 70 families segregating Barrett’s oesophagus and oesophageal adenocarcinoma. J Med Genet 40:651–656

    PubMed  CAS  Google Scholar 

  • Eads CA, Lord RV, Wickramasinghe K, Long TI, Kurumboor SK, Bernstein L, Peters JH, De­Meester SR, DeMeester TR, Skinner KA, Laird PW (2001) Epigenetic patterns in the ­progression of esophageal adenocarcinoma. Cancer Res 61:3410–3418

    PubMed  CAS  Google Scholar 

  • Eda A, Osawa H, Satoh K, Yanaka I, Kihira K, Ishino Y, Mutoh H, Sugano K (2003) Aberrant expression of CDX2 in Barrett’s epithelium and inflammatory esophageal mucosa. J Gastroenterol 38:14–22

    PubMed  CAS  Google Scholar 

  • Fass R, Sampliner RE (2000) Extension of squamous epithelium into the proximal stomach: a newly recognized mucosal abnormality. Endoscopy 32:27–32

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Fitzgerald RC (2006) Molecular basis of Barrett’s oesophagus and oesophageal adenocarcinoma. Gut 55:1810–1820

    PubMed  CAS  Google Scholar 

  • Fountoulakis A, Martin IG, White KL, Dixon MF, Cade JE, Sue-Ling HM, Wild CP (2004) Plasma and esophageal mucosal levels of vitamin C: role in the pathogenesis and neoplastic progression of Barrett’s esophagus. Dig Dis Sci 49:914–919

    PubMed  CAS  Google Scholar 

  • Galipeau PC, Cowan DS, Sanchez CA, Barrett MT, Emond MJ, Levine DS, Rabinovitch PS, Reid BJ (1996) 17p (p53) allelic losses, 4N (G2/tetraploid) populations, and progression to aneuploidy in Barrett’s esophagus. Proc Natl Acad Sci USA 93:7081–7084

    PubMed  CAS  Google Scholar 

  • Garrigue-Antar L, Souza RF, Vellucci VF, Meltzer SJ, Reiss M (1996) Loss of transforming growth factor-beta type II receptor gene expression in primary human esophageal cancer. Lab Invest 75:263–272

    PubMed  CAS  Google Scholar 

  • Geboes K, Desmet V (1978) Histology of the esophagus. Front Gastrointest Res 3:1–17

    PubMed  CAS  Google Scholar 

  • Giaccia AJ, Kastan MB (1998) The complexity of p53 modulation: emerging patterns from divergent signals. Genes Dev 12:2973–2983

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • GOSPE (1991) Barrett’s esophagus: epidemiological and clinical results of a multicentric survey. Gruppo Operativo per lo Studio delle Pre­cancerosi dell’Esofago (GOSPE). Int J Cancer 48:364–368

    Google Scholar 

  • Greaves LC, Preston SL, Tadrous PJ, Taylor RW, Barron MJ, Oukrif D, Leedham SJ, Deheragoda M, Sasieni P, Novelli MR, Jankowski JA, Turnbull DM, Wright NA, McDonald SA (2006) Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission. Proc Natl Acad Sci USA 103:714–719

    PubMed  CAS  Google Scholar 

  • Gronemeyer H, Miturski R (2001) Molecular mechanisms of retinoid action. Cell Mol Biol Lett 6:3–52

    PubMed  CAS  Google Scholar 

  • Guillem PG (2005) How to make a Barrett esophagus: pathophysiology of columnar metaplasia of the esophagus. Dig Dis Sci 50:415–424

    PubMed  Google Scholar 

  • Haggitt RC (1994) Barrett’s esophagus, dysplasia, and adenocarcinoma. Hum Pathol 25:982–993

    PubMed  CAS  Google Scholar 

  • Haggitt RC (2000) Pathology of Barrett’s esophagus. J Gastrointest Surg 4:117–118

    PubMed  CAS  Google Scholar 

  • Haggitt RC, Reid BJ, Rabinovitch PS, Rubin CE (1988) Barrett’s esophagus. Correlation between mucin histochemistry, flow cytometry, and histologic diagnosis for predicting increased cancer risk. Am J Pathol 131:53–61

    PubMed  CAS  Google Scholar 

  • Hamelin R, Flejou JF, Muzeau F, Potet F, Laurent-Puig P, Fekete F, Thomas G (1994) TP53 gene mutations and p53 protein immunoreactivity in malignant and premalignant Barrett’s esophagus. Gastroenterology 107:1012–1018

    PubMed  CAS  Google Scholar 

  • Hampel H, Abraham NS, El-Serag HB (2005) Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications. Ann Intern Med 143:199–211

    PubMed  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    PubMed  CAS  Google Scholar 

  • Hanby AM, Wright NA (1993) The ulcer-associated cell lineage: the gastrointestinal repair kit? J Pathol 171:3–4

    PubMed  CAS  Google Scholar 

  • Hanby AM, Jankowski JA, Elia G, Poulsom R, Wright NA (1994) Expression of the trefoil peptides pS2 and human spasmolytic polypeptide (hSP) in Barrett’s metaplasia and the native oesophageal epithelium: delineation of epithelial phenotype. J Pathol 173:213–219

    PubMed  CAS  Google Scholar 

  • Harmon JW, Johnson LF, Maydonovitch CL (1981) Effects of acid and bile salts on the rabbit esophageal mucosa. Dig Dis Sci 26:65–72

    PubMed  CAS  Google Scholar 

  • Hay ED, Zuk A (1995) Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced. Am J Kidney Dis 26:678–690

    PubMed  CAS  Google Scholar 

  • Hayward J (1961) The treatment of fibrous stricture of the oesophagus associated with hiatal hernia. Thorax 16:45–55

    PubMed  CAS  Google Scholar 

  • Herrera LJ, El-Hefnawy T, Queiroz de Oliveira PE, Raja S, Finkelstein S, Gooding W, Luketich JD, Godfrey TE, Hughes SJ (2005) The HGF receptor c-Met is overexpressed in esophageal adenocarcinoma. Neoplasia 7:75–84

    PubMed  CAS  Google Scholar 

  • Hiyama T, Yoshihara M, Tanaka S, Chayama K (2007) Genetic polymorphisms and esophageal cancer risk. Int J Cancer 121:1643–1658

    PubMed  CAS  Google Scholar 

  • Hopwood D, Milne G, Logan KR (1979) Electron microscopic changes in human oesophageal epithelium in oesophagitis. J Pathol 129:161–167

    PubMed  CAS  Google Scholar 

  • Iascone C, DeMeester TR, Little AG, Skinner DB (1983) Barrett’s esophagus. Functional assessment, proposed pathogenesis, and surgical therapy. Arch Surg 118:543–549

    PubMed  CAS  Google Scholar 

  • Iijima K, Grant J, McElroy K, Fyfe V, Preston T, McColl KE (2003) Novel mechanism of nitrosative stress from dietary nitrate with relevance to gastro-oesophageal junction cancers. Carcinogenesis 24:1951–1960

    PubMed  CAS  Google Scholar 

  • Ireland AP, Shibata DK, Chandrasoma P, Lord RV, Peters JH, DeMeester TR (2000) Clinical significance of p53 mutations in adenocarcinoma of the esophagus and cardia. Ann Surg 231:179–187

    PubMed  CAS  Google Scholar 

  • Jankowski J, Hoopwood D, Dover R, Wormsley KG (1992) Development and growth of normal, metaplastic and dysplastic oesophageal mucosa: biological markers of neoplasia. Eur J Gas­troeneterol Hepatol 5:12

    Google Scholar 

  • 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 

  • Jankowski JA, Harrison RF, Perry I, Balkwill F, Tselepis C (2000) Barrett’s metaplasia. Lancet 356:2079–2085

    PubMed  CAS  Google Scholar 

  • Jiang WG, Martin TA, Parr C, Davies G, Matsumoto K, Nakamura T (2005) Hepatocyte growth factor, its receptor, and their potential value in cancer therapies. Crit Rev Oncol Hematol 53:35–69

    PubMed  Google Scholar 

  • Jimenez P, Piazuelo E, Sanchez MT, Ortego J, Soteras F, Lanas A (2005) Free radicals and ­antioxidant systems in reflux esophagitis and Barrett’s esophagus. World J Gastroenterol 11:2697–2703

    PubMed  CAS  Google Scholar 

  • Johansson J, Hakansson HO, Mellblom L, Kempas A, Johansson KE, Granath F, Nyren O (2007) Risk factors for Barrett’s oesophagus: a population-based approach. Scand J Gastroenterol 42:148–156

    PubMed  Google Scholar 

  • Johns BA (1952) Developmental changes in the oesophageal epithelium in man. J Anat 86:431–442

    PubMed  CAS  Google Scholar 

  • Jones BE, Lo CR, Liu H, Pradhan Z, Garcia L, Srinivasan A, Valentino KL, Czaja MJ (2000) Role of caspases and NF-kappaB signaling in hydrogen peroxide- and superoxide-induced hepatocyte apoptosis. Am J Physiol Gastrointest Liver Physiol 278:G693–G699

    PubMed  CAS  Google Scholar 

  • Kauer WK, Peters JH, DeMeester TR, Ireland AP, Bremner CG, Hagen JA (1995) Mixed reflux of gastric and duodenal juices is more harmful to the esophagus than gastric juice alone. The need for surgical therapy re-emphasized. Ann Surg 222:525–531; discussion 531–523

    Google Scholar 

  • Kawakami K, Brabender J, Lord RV, Groshen S, Greenwald BD, Krasna MJ, Yin J, Fleisher AS, Abraham JM, Beer DG, Sidransky D, Huss HT, Demeester TR, Eads C, Laird PW, Ilson DH, Kelsen DP, Harpole D, Moore MB, Danenberg KD, Danenberg PV, Meltzer SJ (2000) Hyper­methylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma. J Natl Cancer Inst 92:1805–1811

    PubMed  CAS  Google Scholar 

  • Kerkhof M, Kusters JG, van Dekken H, Kuipers EJ, Siersema PD (2007) Biomarkers for risk stratification of neoplastic progression in Barrett esophagus. Cell Oncol 29:507–517

    PubMed  CAS  Google Scholar 

  • Khalbuss WE, Marousis CG, Subramanyam M, Orlando RC (1995) Effect of HCl on transmembrane potentials and intracellular pH in rabbit esophageal epithelium. Gastroenterology 108:662–672

    PubMed  CAS  Google Scholar 

  • Kivilaakso E, Fromm D, Silen W (1980) Effect of bile salts and related compounds on isolated esophageal mucosa. Surgery 87:280–285

    PubMed  CAS  Google Scholar 

  • Klump B, Hsieh CJ, Holzmann K, Gregor M, Porschen R (1998) Hypermethylation of the CDKN2/p16 promoter during neoplastic progression in Barrett’s esophagus. Gastroenterology 115:1381–1386

    PubMed  CAS  Google Scholar 

  • Koike N, Higuchi T, Sakai Y (1990) Goblet-like cells in atrophic vaginal smears and their histologic correlation. Possible confusion with endocervical cells. Acta Cytol 34:785–788

    PubMed  CAS  Google Scholar 

  • Krishnadath KK, Tilanus HW, van Blankenstein M, Hop WC, Kremers ED, Dinjens WN, Bosman FT (1997) Reduced expression of the cadherin-catenin complex in oesophageal adenocarcinoma correlates with poor prognosis. J Pathol 182:331–338

    PubMed  CAS  Google Scholar 

  • Kubo A, Levin TR, Block G, Rumore GJ, Que­senberry CP Jr, Buffler P, Corley DA (2008) Dietary patterns and the risk of Barrett’s esophagus. Am J Epidemiol 167:839–846

    PubMed  Google Scholar 

  • Kyrgidis A, Kountouras J, Zavos C, Chatzopoulos D (2005) New molecular concepts of Barrett’s esophagus: clinical implications and biomarkers. J Surg Res 125:189–212

    PubMed  CAS  Google Scholar 

  • Lagarde SM, ten Kate FJ, Richel DJ, Offerhaus GJ, van Lanschot JJ (2007) Molecular prognostic factors in adenocarcinoma of the esophagus and gastroesophageal junction. Ann Surg Oncol 14:977–991

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Lin L, Prescott MS, Zhu Z, Singh P, Chun SY, Kuick RD, Hanash SM, Orringer MB, Glover TW, Beer DG (2000) Identification and characterization of a 19q12 amplicon in esophageal adenocarcinomas reveals cyclin E as the best candidate gene for this amplicon. Cancer Res 60:7021–7027

    PubMed  CAS  Google Scholar 

  • Liu RH, Hotchkiss JH (1995) Potential genotoxicity of chronically elevated nitric oxide: a review. Mutat Res 339:73–89

    PubMed  CAS  Google Scholar 

  • Lord RV, Salonga D, Danenberg KD, Peters JH, DeMeester TR, Park JM, Johansson J, Skinner KA, Chandrasoma P, DeMeester SR, Bremner CG, Tsai PI, Danenberg PV (2000) Telomerase reverse transcriptase expression is increased early in the Barrett’s metaplasia, dysplasia, adenocarcinoma sequence. J Gastrointest Surg 4:135–142

    PubMed  CAS  Google Scholar 

  • Lord RV, Brabender J, Wickramasinghe K, DeMeester SR, Holscher A, Schneider PM, Danenberg PV, DeMeester TR (2005) Increased CDX2 and decreased PITX1 homeobox gene expression in Barrett’s esophagus and Barrett’s-associated adenocarcinoma. Surgery 138:924–931

    PubMed  Google Scholar 

  • Maley CC, Reid BJ (2005) Natural selection in neoplastic progression of Barrett’s esophagus. Semin Cancer Biol 15:474–483

    PubMed  CAS  Google Scholar 

  • Maley CC, Galipeau PC, Li X, Sanchez CA, Paulson TG, Reid BJ (2004) Selectively advantageous mutations and hitchhikers in neoplasms: p16 lesions are selected in Barrett’s esophagus. Cancer Res 64:3414–3427

    PubMed  CAS  Google Scholar 

  • Malfertheiner P, Peitz U (2005) The interplay between Helicobacter pylori, gastro-oesophageal reflux disease, and intestinal metaplasia. Gut 54(Suppl 1):i13–i20

    PubMed  Google Scholar 

  • Marshall RE, Anggiansah A, Owen WA, Owen WJ (1997) The relationship between acid and bile reflux and symptoms in gastro-oesophageal reflux disease. Gut 40:182–187

    PubMed  CAS  Google Scholar 

  • Mates JM, Perez-Gomez C, Nunez de Castro I (1999) Antioxidant enzymes and human diseases. Clin Biochem 32:595–603

    PubMed  CAS  Google Scholar 

  • McColl KE (2005) When saliva meets acid: chemical warfare at the oesophagogastric junction. Gut 54:1–3

    PubMed  CAS  Google Scholar 

  • Menke-Pluymers MB, Mulder AH, Hop WC, van Blankenstein M, Tilanus HW (1994) Dysplasia and aneuploidy as markers of malignant degeneration in Barrett’s oesophagus. The Rotterdam Oesophageal Tumour Study Group. Gut 35:1348–1351

    PubMed  CAS  Google Scholar 

  • Milano F, van Baal JW, Buttar NS, Rygiel AM, de Kort F, DeMars CJ, Rosmolen WD, Bergman JJ, VAM J, Wang KK, Peppelenbosch MP, Kris­hnadath KK (2007) Bone morphogenetic protein 4 expressed in esophagitis induces a columnar phenotype in esophageal squamous cells. Gastroenterology 132:2412–2421

    PubMed  CAS  Google Scholar 

  • Mittal RK, Balaban DH (1997) The esophagogastric junction. N Engl J Med 336:924–932

    PubMed  CAS  Google Scholar 

  • Mittal RK, Lange RC, McCallum RW (1987) Identification and mechanism of delayed esophageal acid clearance in subjects with hiatus hernia. Gastroenterology 92:130–135

    PubMed  CAS  Google Scholar 

  • Moayyedi P (2008) Barrett’s esophagus and obesity: the missing part of the puzzle. Am J Gastroenterol 103:301–303

    PubMed  Google Scholar 

  • Mobius C, Stein HJ, Becker I, Feith M, Theisen J, Gais P, Jutting U, Siewert JR (2003) The ‘angiogenic switch’ in the progression from Barrett’s metaplasia to esophageal adenocarcinoma. Eur J Surg Oncol 29:890–894

    PubMed  CAS  Google Scholar 

  • Mobius C, Stein HJ, Spiess C, Becker I, Feith M, Theisen J, Gais P, Jutting U, Siewert JR (2005) COX2 expression, angiogenesis, proliferation and survival in Barrett’s cancer. Eur J Surg Oncol 31:755–759

    PubMed  CAS  Google Scholar 

  • Moersch RN, Ellis FH Jr, Mc DJ (1959) Pathologic changes occurring in severe reflux esophagitis. Surg Gynecol Obstet 108:476–484

    PubMed  CAS  Google Scholar 

  • Montgomery EA, Hartmann DP, Carr NJ, Holterman DA, Sobin LH, Azumi N (1996) Barrett eso­phagus with dysplasia. Flow cytometric DNA analysis of routine, paraffin-embedded mucosal bio­psies. Am J Clin Pathol 106:298–304

    PubMed  CAS  Google Scholar 

  • Montgomery RK, Mulberg AE, Grand RJ (1999) Development of the human gastrointestinal tract: twenty years of progress. Gastroenterology 116:702–731

    PubMed  CAS  Google Scholar 

  • Moons LM, Bax DA, Kuipers EJ, Van Dekken H, Haringsma J, Van Vliet AH, Siersema PD, Kusters JG (2004) The homeodomain protein CDX2 is an early marker of Barrett’s oesophagus. J Clin Pathol 57:1063–1068

    PubMed  CAS  Google Scholar 

  • Morales CP, Souza RF, Spechler SJ (2002) Hall­marks of cancer progression in Barrett’s oesophagus. Lancet 360:1587–1589

    PubMed  Google Scholar 

  • Morris CD, Armstrong GR, Bigley G, Green H, Attwood SE (2001) Cyclooxygenase-2 expression in the Barrett’s metaplasia-dysplasia-adenocarcinoma sequence. Am J Gastroenterol 96:990–996

    PubMed  CAS  Google Scholar 

  • Murray AW (2004) Recycling the cell cycle: cyclins revisited. Cell 116:221–234

    PubMed  CAS  Google Scholar 

  • Nair KS, Naidoo R, Chetty R (2005) Expression of cell adhesion molecules in oesophageal carcinoma and its prognostic value. J Clin Pathol 58:343–351

    PubMed  CAS  Google Scholar 

  • Nehra D, Howell P, Williams CP, Pye JK, Beynon J (1999) Toxic bile acids in gastro-oesophageal reflux disease: influence of gastric acidity. Gut 44:598–602

    PubMed  CAS  Google Scholar 

  • Neumann CS, Cooper BT (1994) 24 hour ambulatory oesophageal pH monitoring in uncomplicated Barrett’s oesophagus. Gut 35:1352–1355

    PubMed  CAS  Google Scholar 

  • O’Riordan JM, Abdel-latif MM, Ravi N, McNamara D, Byrne PJ, McDonald GS, Keeling PW, Kelleher D, Reynolds JV (2005) Proinflammatory cytokine and nuclear factor kappa-B expression along the inflammation-metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. Am J Gastroenterol 100:1257–1264

    PubMed  Google Scholar 

  • Olliver JR, Hardie LJ, Gong Y, Dexter S, Chalmers D, Harris KM, Wild CP (2005) Risk factors, DNA damage, and disease progression in Bar­rett’s esophagus. Cancer Epidemiol Biomarkers Prev 14:620–625

    PubMed  CAS  Google Scholar 

  • Park YS, Park HJ, Kang GH, Kim CJ, Chi JG (2003) Histology of gastroesophageal junction in fetal and pediatric autopsy. Arch Pathol Lab Med 127:451–455

    PubMed  Google Scholar 

  • Paull A, Trier JS, Dalton MD, Camp RC, Loeb P, Goyal RK (1976) The histologic pectrum of Barrett’s esophagus. N Engl J Med 295:476–480

    PubMed  CAS  Google Scholar 

  • Pera M, Brito MJ, Poulsom R, Riera E, Grande L, Hanby A, Wright NA (2000) Duodenal-content reflux esophagitis induces the development of glandular metaplasia and adenosquamous carcinoma in rats. Carcinogenesis 21:1587–1591

    PubMed  CAS  Google Scholar 

  • Phillips RW, Frierson HF Jr, Moskaluk CA (2003) Cdx2 as a marker of epithelial intestinal ­differentiation in the esophagus. Am J Surg Pathol 27:1442–1447

    PubMed  Google Scholar 

  • Powell SM, Papadopoulos N, Kinzler KW, Smo­linski KN, Meltzer SJ (1994) APC gene mutations in the mutation cluster region are rare in esophageal cancers. Gastroenterology 107:1759–1763

    PubMed  CAS  Google Scholar 

  • Prives C, Hall PA (1999) The p53 pathway. J Pathol 187:112–126

    PubMed  CAS  Google Scholar 

  • Radominska-Pandya A, Chen G (2002) Photoaffinity labeling of human retinoid X receptor beta (RXRbeta) with 9-cis-retinoic acid: identification of phytanic acid, docosahexaenoic acid, and lithocholic acid as ligands for RXRbeta. Bio­chemistry 41:4883–4890

    PubMed  CAS  Google Scholar 

  • Rastogi A, Puli S, El-Serag HB, Bansal A, Wani S, Sharma P (2008) Incidence of esophageal adenocarcinoma in patients with Barrett’s esophagus and high-grade dysplasia: a meta-analysis. Gastrointest Endosc 67:394–398

    PubMed  Google Scholar 

  • Rees JR, Onwuegbusi BA, Save VE, Alderson D, Fitzgerald RC (2006) In vivo and in vitro evidence for transforming growth factor-beta1-mediated epithelial to mesenchymal transition in esophageal adenocarcinoma. Cancer Res 66:9583–9590

    PubMed  CAS  Google Scholar 

  • Ribeiro U Jr, Finkelstein SD, Safatle-Ribeiro AV, Landreneau RJ, Clarke MR, Bakker A, Swalsky PA, Gooding WE, Posner MC (1998) p53 sequence analysis predicts treatment response and outcome of patients with esophageal carcinoma. Cancer 83:7–18

    PubMed  CAS  Google Scholar 

  • Richter JE (2000) Importance of bile reflux in Barrett’s esophagus. Dig Dis 18:208–216

    PubMed  Google Scholar 

  • Robert V, Michel P, Flaman JM, Chiron A, Martin C, Charbonnier F, Paillot B, Frebourg T (2000) High frequency in esophageal cancers of p53 alterations inactivating the regulation of genes involved in cell cycle and apoptosis. Car­cinogenesis 21:563–565

    PubMed  CAS  Google Scholar 

  • Rochat A, Kobayashi K, Barrandon Y (1994) Location of stem cells of human hair follicles by clonal analysis. Cell 76:1063–1073

    PubMed  CAS  Google Scholar 

  • Romero Y, Cameron AJ, Locke GR 3rd, Schaid DJ, Slezak JM, Branch CD, Melton LJ 3rd (1997) Familial aggregation of gastroesophageal reflux in patients with Barrett’s esophagus and esophageal adenocarcinoma. Gastroenterology 113:1449–1456

    PubMed  CAS  Google Scholar 

  • Safaie-Shirazi S (1977) Effect of pepsin on ionic permeability of canine esophageal mucosa. J Surg Res 22:5–8

    PubMed  CAS  Google Scholar 

  • Salo JA, Lehto VP, Kivilaakso E (1983) Mor­phological alterations in experimental esophagitis. Light microscopic and scanning and trans­mission electron microscopic study. Dig Dis Sci 28:440–448

    PubMed  CAS  Google Scholar 

  • Sampliner RE (1998) 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 93:1028–1032

    PubMed  CAS  Google Scholar 

  • Sappati Biyyani RS, Chessler L, McCain E, Nelson K, Fahmy N, King J (2007) Familial trends of inheritance in gastro esophageal reflux disease, Barrett’s esophagus and Barrett’s adenocarcinoma: 20 families. Dis Esophagus 20:53–57

    PubMed  CAS  Google Scholar 

  • Sarbia M, Bektas N, Muller W, Heep H, Borchard F, Gabbert HE (1999) Expression of cyclin E in dysplasia, carcinoma, and nonmalignant lesions of Barrett esophagus. Cancer 86:2597–2601

    PubMed  CAS  Google Scholar 

  • Sarosi G, Brown G, Jaiswal K, Feagins LA, Lee E, Crook TW, Souza RF, Zou YS, Shay JW, Spechler SJ (2008) Bone marrow progenitor cells contribute to esophageal regeneration and metaplasia in a rat model of Barrett’s esophagus. Dis Esophagus 21:43–50

    PubMed  CAS  Google Scholar 

  • Sawhney RA, Shields HM, Allan CH, Boch JA, Trier JS, Antonioli DA (1996) Morphological characterization of the squamocolumnar junction of the esophagus in patients with and without Barrett’s epithelium. Dig Dis Sci 41:1088–1098

    PubMed  CAS  Google Scholar 

  • Schmidt PH, Lee JR, Joshi V, Playford RJ, Poulsom R, Wright NA, Goldenring JR (1999) Identification of a metaplastic cell lineage associated with human gastric adenocarcinoma. Lab Invest 79:639–646

    PubMed  CAS  Google Scholar 

  • Schneider PM, Stoeltzing O, Roth JA, Hoelscher AH, Wegerer S, Mizumoto S, Becker K, Dittler HJ, Fink U, Siewert JR (2000) P53 mutational status improves estimation of prognosis in patients with curatively resected adenocarcinoma in Barrett’s esophagus. Clin Cancer Res 6:3153–3158

    PubMed  CAS  Google Scholar 

  • Schorah CJ, Sobala GM, Sanderson M, Collis N, Primrose JN (1991) Gastric juice ascorbic acid: effects of disease and implications for gastric carcinogenesis. Am J Clin Nutr 53:287S–293S

    PubMed  CAS  Google Scholar 

  • Seery JP (2002) Stem cells of the oesophageal epithelium. J Cell Sci 115:1783–1789

    PubMed  Google Scholar 

  • Seery JP, Watt FM (2000) Asymmetric stem-cell divisions define the architecture of human oesophageal epithelium. Curr Biol 10:1447–1450

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Shay JW, Bacchetti S (1997) A survey of telomerase activity in human cancer. Eur J Cancer 33:787–791

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Shirvani VN, Ouatu-Lascar R, Kaur BS, Omary MB, Triadafilopoulos G (2000) Cyclooxygenase 2 expression in Barrett’s esophagus and adenocarcinoma: Ex vivo induction by bile salts and acid exposure. Gastroenterology 118:487–496

    PubMed  CAS  Google Scholar 

  • Singh AB, Harris RC (2005) Autocrine, paracrine and juxtacrine signaling by EGFR ligands. Cell Signal 17:1183–1193

    PubMed  CAS  Google Scholar 

  • Singh P, Taylor RH, Colin-Jones DG (1994) Esophageal motor dysfunction and acid exposure in reflux esophagitis are more severe if Barrett’s metaplasia is present. Am J Gas­troenterol 89:349–356

    PubMed  CAS  Google Scholar 

  • Sital RR, Kusters JG, De Rooij FW, Kuipers EJ, Siersema PD (2006) Bile acids and Barrett’s oesophagus: a sine qua non or coincidence? Scand J Gastroenterol Suppl:11–17

    Google Scholar 

  • Slack JM (2000) Stem cells in epithelial tissues. Science 287:1431–1433

    PubMed  CAS  Google Scholar 

  • Sloan S, Kahrilas PJ (1991) Impairment of esophageal emptying with hiatal hernia. Gastroenterology 100:596–605

    PubMed  CAS  Google Scholar 

  • Sloan S, Rademaker AW, Kahrilas PJ (1992) Deter­minants of gastroesophageal junction incompetence: hiatal hernia, lower esophageal sphincter, or both? Ann Intern Med 117:977–982

    PubMed  CAS  Google Scholar 

  • Smedts F, Ramaekers FC, Vooijs PG (1993) The dynamics of keratin expression in malignant transformation of cervical epithelium: a review. Obstet Gynecol 82:465

    PubMed  CAS  Google Scholar 

  • Sodhani P, Gupta S, Prakash S, Singh V (1999) Columnar and metaplastic cells in vault smears: cytologic and colposcopic study. Cytopathology 10:122–126; discussion 131

    Google Scholar 

  • Souza RF, Garrigue-Antar L, Lei J, Yin J, Appel R, Vellucci VF, Zou TT, Zhou X, Wang S, Rhyu MG, Cymes K, Chan O, Park WS, Krasna MJ, Greenwald BD, Cottrell J, Abraham JM, Simms L, Leggett B, Young J, Harpaz N, Reiss M, Meltzer SJ (1996) Alterations of transforming growth factor-beta 1 receptor type II occur in ulcerative colitis-associated carcinomas, sporadic colorectal neoplasms, and esophageal carcinomas, but not in gastric neoplasms. Hum Cell 9:229–236

    PubMed  CAS  Google Scholar 

  • Souza RF, Morales CP, Spechler SJ (2001) Review article: a conceptual approach to understanding the molecular mechanisms of cancer development in Barrett’s oesophagus. Aliment Pharmacol Ther 15:1087–1100

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Stein HJ, Siewert JR (1993) Barrett’s esophagus: pathogenesis, epidemiology, functional abnormalities, malignant degeneration, and surgical management. Dysphagia 8:276–288

    PubMed  CAS  Google Scholar 

  • Stein HJ, DeMeester TR, Naspetti R, Jamieson J, Perry RE (1991) Three-dimensional imaging of the lower esophageal sphincter in gastroesophageal reflux disease. Ann Surg 214:374–383; discussion 383–374

    Google Scholar 

  • Stein HJ, Barlow AP, DeMeester TR, Hinder RA (1992) Complications of gastroesophageal re­flux disease. Role of the lower esophageal sphincter, esophageal acid and acid/alkaline exposure, and duodenogastric reflux. Ann Surg 216:35–43

    PubMed  CAS  Google Scholar 

  • Suzuki H, Iijima K, Scobie G, Fyfe V, McColl KE (2005) Nitrate and nitrosative chemistry within Barrett’s oesophagus during acid reflux. Gut 54:1527–1535

    PubMed  CAS  Google Scholar 

  • Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2:442–454

    PubMed  CAS  Google Scholar 

  • Thiery JP (2003) Epithelial-mesenchymal transitions in development and pathologies. Curr Opin Cell Biol 15:740–746

    PubMed  CAS  Google Scholar 

  • Thomas T, Abrams KR, De Caestecker JS, Robinson RJ (2007) Meta analysis: cancer risk in Barrett’s oesophagus. Aliment Pharmacol Ther 26:1465–1477

    PubMed  CAS  Google Scholar 

  • Tosh D, Slack JM (2002) How cells change their phenotype. Nat Rev Mol Cell Biol 3:187–194

    PubMed  CAS  Google Scholar 

  • Tuynman JB, Buskens CJ, Kemper K, ten Kate FJ, Offerhaus GJ, Richel DJ, van Lanschot JJ (2005) Neoadjuvant selective COX-2 inhibition down-regulates important oncogenic pathways in patients with esophageal adenocarcinoma. Ann Surg 242:840–849, discussion 849–850

    Google Scholar 

  • Tuynman JB, Lagarde SM, Ten Kate FJ, Richel DJ, van Lanschot JJ (2008) Met expression is an independent prognostic risk factor in patients with oesophageal adenocarcinoma. Br J Cancer 98:1102–1108

    PubMed  CAS  Google Scholar 

  • Tytgat GN (1995) Does endoscopic surveillance in esophageal columnar metaplasia (Barrett’s eso­phagus) have any real value? Endoscopy 27:19–26

    PubMed  CAS  Google Scholar 

  • Vaezi MF, Richter JE (1995) Synergism of acid and duodenogastroesophageal reflux in complicated Barrett’s esophagus. Surgery 117:699–704

    PubMed  CAS  Google Scholar 

  • Vaezi MF, Richter JE (1996) Role of acid and duodenogastroesophageal reflux in gastroesophageal reflux disease. Gastroenterology 111:1192–1199

    PubMed  CAS  Google Scholar 

  • van Baal JW, Milano F, Rygiel AM, Bergman JJ, Rosmolen WD, van Deventer SJ, Wang KK, Peppelenbosch MP, Krishnadath KK (2005) A comparative analysis by SAGE of gene expression profiles of Barrett’s esophagus, normal squamous esophagus, and gastric cardia. Gas­troenterology 129:1274–1281

    PubMed  Google Scholar 

  • van Baal JW, Bozikas A, Pronk R, Ten Kate FJ, Milano F, Rygiel AM, Rosmolen WD, Peppelenbosch MP, Bergman JJ, Krishnadath KK (2008) Cytokeratin and CDX-2 expression in Barrett’s esophagus. Scand J Gastroenterol 43:132–140

    PubMed  Google Scholar 

  • Vizcaino AP, Moreno V, Lambert R, Parkin DM (2002) Time trends incidence of both major histologic types of esophageal carcinomas in selected countries, 1973-1995. Int J Cancer 99:860–868

    PubMed  CAS  Google Scholar 

  • von Rahden BH, Stein HJ, Feith M, Puhringer F, Theisen J, Siewert JR, Sarbia M (2006) Overexpression of TGF-beta1 in esophageal (Barrett’s) adenocarcinoma is associated with advanced stage of disease and poor prognosis. Mol Carcinog 45:786–794

    Google Scholar 

  • Wang KL, Wu TT, Choi IS, Wang H, Reseetkova E, Correa AM, Hofstetter WL, Swisher SG, Ajani JA, Rashid A, Albarracin CT (2007) Expression of epidermal growth factor receptor in esophageal and esophagogastric junction adenocarcinomas: association with poor outcome. Cancer 109:658–667

    PubMed  CAS  Google Scholar 

  • Wetscher GJ, Hinder RA, Bagchi D, Hinder PR, Bagchi M, Perdikis G, McGinn T (1995) Reflux esophagitis in humans is mediated by oxygen-derived free radicals. Am J Surg 170:552–556; discussion 556–557

    Google Scholar 

  • Wijnhoven BP, Dinjens WN, Pignatelli M (2000) E-cadherin-catenin cell-cell adhesion complex and human cancer. Br J Surg 87:992–1005

    PubMed  CAS  Google Scholar 

  • Wijnhoven BP, Tilanus HW, Dinjens WN (2001) Molecular biology of Barrett’s adenocarcinoma. Ann Surg 233:322–337

    PubMed  CAS  Google Scholar 

  • Wild CP, Hardie LJ (2003) Reflux, Barrett’s oesophagus and adenocarcinoma: burning questions. Nat Rev Cancer 3:676–684

    PubMed  CAS  Google Scholar 

  • Wilkinson NW, Black JD, Roukhadze E, Driscoll D, Smiley S, Hoshi H, Geradts J, Javle M, Brattain M (2004) Epidermal growth factor receptor expression correlates with histologic grade in resected esophageal adenocarcinoma. J Gas­trointest Surg 8:448–453

    PubMed  Google Scholar 

  • Williams LJ, Guernsey DL, Casson AG (2006) Biomarkers in the molecular pathogenesis of esophageal (Barrett) adenocarcinoma. Curr Oncol 13:33–43

    PubMed  CAS  Google Scholar 

  • Wilson KT, Fu S, Ramanujam KS, Meltzer SJ (1998) Increased expression of inducible nitric oxide synthase and cyclooxygenase-2 in Barrett’s esophagus and associated adenocarcinomas. Cancer Res 58:2929–2934

    PubMed  CAS  Google Scholar 

  • Winters C Jr, Spurling TJ, Chobanian SJ, Curtis DJ, Esposito RL, Hacker JF 3rd, Johnson DA, Cruess DF, Cotelingam JD, Gurney MS et al (1987) Barrett’s esophagus. A prevalent, occult complication of gastroesophageal reflux disease. Gastroenterology 92:118–124

    PubMed  Google Scholar 

  • Wright NA (1996) Migration of the ductular elements of gut-associated glands gives clues to the histogenesis of structures associated with responses to acid hypersecretory state: the origins of “gastric metaplasia” in the duodenum of the specialized mucosa of Barrett’s esophagus and of pseudopyloric metaplasia. Yale J Biol Med 69:147–153

    PubMed  CAS  Google Scholar 

  • Yacoub L, Goldman H, Odze RD (1997) Trans­forming growth factor-alpha, epidermal growth factor receptor, and MiB-1 expression in Barrett’s-associated neoplasia: correlation with prognosis. Mod Pathol 10:105–112

    PubMed  CAS  Google Scholar 

  • Yamamoto Y, Gaynor RB (2001) Therapeutic potential of inhibition of the NF-kappaB pathway in the treatment of inflammation and cancer. J Clin Invest 107:135–142

    PubMed  CAS  Google Scholar 

  • Yamamoto K, Arakawa T, Ueda N, Yamamoto S (1995) Transcriptional roles of nuclear factor kappa B and nuclear factor-interleukin-6 in the tumor necrosis factor alpha-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells. J Biol Chem 270:31315–31320

    PubMed  CAS  Google Scholar 

  • Younes M, Lebovitz RM, Lechago LV, Lechago J (1993) p53 protein accumulation in Barrett’s metaplasia, dysplasia, and carcinoma: a follow-up study. Gastroenterology 105:1637–1642

    PubMed  CAS  Google Scholar 

  • Yousef F, Cardwell C, Cantwell MM, Galway K, Johnston BT, Murray L (2008) The incidence of esophageal cancer and high-grade dysplasia in Barrett’s esophagus: a systematic review and meta-analysis. Am J Epidemiol 168:237–249

    PubMed  Google Scholar 

  • Yu WY, Slack JM, Tosh D (2005) Conversion of columnar to stratified squamous epithelium in the developing mouse oesophagus. Dev Biol 284:157–170

    PubMed  CAS  Google Scholar 

  • Yusuf S, Hawken S, Ounpuu S, Bautista L, Franzosi MG, Commerford P, Lang CC, Rumboldt Z, Onen CL, Lisheng L, Tanomsup S, Wangai P Jr, Razak F, Sharma AM, Anand SS (2005) Obesity and the risk of myocardial infarction in 27, 000 participants from 52 countries: a case-control study. Lancet 366:1640–1649

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Brechtje A. Grotenhuis .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Grotenhuis, B.A., van Lanschot, J.J.B., Dinjens, W.N.M., Wijnhoven, B.P.L. (2009). The Pathogenesis of Barrett’s Metaplasia and the Progression to Esophageal Adenocarcinoma. In: Schneider, P. (eds) Adenocarcinoma of the Esophagogastric Junction. Recent Results in Cancer Research, vol 182. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-70579-6_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-70579-6_4

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-70578-9

  • Online ISBN: 978-3-540-70579-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics