Molecular Biology of Adenocarcinoma Arising in Barrett’s Esophagus

  • James D. Mueller
Conference paper


The last several years have seen a rapid rise in the incidence of both Barrett’s esophagus and adenocarcinoma of the distal esophagus [1]. Because most patients with these tumors present late owing to the lack of specific symptoms, the prognostic outlook for most is poor despite improvements in surgical treatment [2,3]. For this reason it has become apparent that successful therapeutic strategies must be based on early detection and treatment. This in turn has brought heightened interest to studying the carcinogenesis of these tumors, as a better understanding of their molecular biology could provide new diagnostic and therapeutic possibilities.


Comparative Genomic Hybridization Esophageal Adenocarcinoma Distal Esophagus Gastric Cardia Adenocarcinoma Chronic Reflux Esophagitis 
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  1. 1.
    Williamson WA, Ellis FH Jr, Gibb SP, Shahian DM, Aretz HT, Heatley GJ, Watkins E Jr (1991) Barrett’s esophagus: prevalence and incidence of adenocarcinoma. Arch Intern Med 151:2212–2216PubMedCrossRefGoogle Scholar
  2. 2.
    Hölscher AH, Bollschweiler E, Bumm R, Bartels H, Siewert JR (1995) Prognostic factors of resected adenocarcinoma of the esophagus. Surgery 118:845–855PubMedCrossRefGoogle Scholar
  3. 3.
    Hoff SJ, Sawyers JL, Blanke CD, Choy H, Stewart JR (1998) Prognosis of adenocarcinoma arising in Barrett’s esophagus. Ann Thorac Surg 65:176–180PubMedCrossRefGoogle Scholar
  4. 4.
    Chen MY, Ott DJ, Gelfand DW (1995) More evidence for the increasing prevalence of adenocarcinoma of the esophagus over an 18-year period. J Clin Gastroenterol 21:254–255PubMedCrossRefGoogle Scholar
  5. 5.
    Levine DS, Haggitt RC, Blount PL, Rabinovitch PS, Rusch VW, Reid BJ (1993) An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett’s esophagus. Gastroenterology 105:40–50PubMedGoogle Scholar
  6. 6.
    Lewin K (1985) Barrett’s esophagus, columnar dysplasia, and adenocarcinoma of the esophagus. In: Tumors of the esophagus and stomach, 2nd edn. Armed Forces Institute of Pathology, Washington, DC, p 99Google Scholar
  7. 7.
    Reid BJ, Haggitt RC, Rubin CE, Roth G, Surawicz CM, Van Belle G, Lewin K, Weinstein WM, Antonioli DA, Goldman H (1988) Observer variation in the diagnosis of dysplasia in Barrett’s esophagus. Hum Pathol 19:166–178PubMedCrossRefGoogle Scholar
  8. 8.
    Hagen JA (1997) Management of Barrett’s esophagus with dysplasia. Semin Thorac Cardiovasc Surg 9:285–289PubMedGoogle Scholar
  9. 9.
    Weinstein WM, Ippoliti AF (1996) The diagnosis of Barrett’s esophagus: goblets, goblets, goblets [editorial]. Gastrointest Endosc 44:91–95PubMedCrossRefGoogle Scholar
  10. 10.
    Rusch VW, Levine DS, Haggitt R, Reid BJ (1994) The management of high grade dysplasia and early cancer in Barrett’s esophagus: a multidisciplinary problem. Cancer 74:1225–1229PubMedCrossRefGoogle Scholar
  11. 11.
    Pera M, Trastek VF, Carpenter HA, Allen MS, Deschamps C, Pairolero PC (1992) Barrett’s esophagus with high-grade dysplasia: an indication for esophagectomy? Ann Thorac Surg 54:199–204PubMedCrossRefGoogle Scholar
  12. 12.
    Hong MK, Laskin WB, Herman BE, Johnston MH, Vargo JJ, Steinberg SM, Allegra CJ, Johnston PG (1995) Expansion of the Ki-67 proliferative compartment correlates with degree of dysplasia in Barrett’s esophagus. Cancer 75:423–429PubMedCrossRefGoogle Scholar
  13. 13.
    Polkowski W, Baak JPA, Van Lanshot JJB, Meijer GA, Schuurmans LT, Ten Kate FJW, Obertrop H, Offerhaus GJA (1998) Clinical decision making in Barrett’s oesophagus can be supported by computerized immunoquantitation and morphometry of features associated with proliferation and differentiation. J Pathol 184:161–168PubMedCrossRefGoogle Scholar
  14. 14.
    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 107:1012–1018PubMedGoogle Scholar
  15. 15.
    Symmans PI, Linehan JM, Brito MJ, Filipe MI (1994) P53 expression in Barrett’s oesophagus, dysplasia, and adenocarcinoma using antibody DO-7. J Pathol 173: 221–226PubMedCrossRefGoogle Scholar
  16. 16.
    Krishnadath KK, Tilanus HW, van Blankenstein M, Bosman FT, Mulder AH (1995) Accumulation of p53 protein in normal, dysplastic, and neoplastic Barrett’s oesophagus. J PathoI175:175–180Google Scholar
  17. 17.
    Casson AG, Manolopoulos B, Troster M, Kerkvliet N, O’Malley F, Inculet R, Finley R, Roth JA (1994) Clinical implications of p53 gene mutation in the progression of Barrett’s epithelium to invasive esophageal cancer. Am J Surg 167:52–57PubMedCrossRefGoogle Scholar
  18. 18.
    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 152:135–144PubMedGoogle Scholar
  19. 19.
    Swami S, Kumble S, Triadafilopoulos G (1995) E-cadherin expression in gastroesophageal reflux disease, Barrett’s esophagus, and esophageal adenocarcinoma: an immunohistochemical and immunoblot study. Am J Gastroenterol 90:1808–1813PubMedGoogle Scholar
  20. 20.
    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 182:331–338PubMedCrossRefGoogle Scholar
  21. 21.
    Walch AK, Zitzelsberger HF, Bruch J, Keller G, Angermeier D, Aubele MM, Mueller JD, Stein H, Braselmann H, Siewert JR, Hofler H, Werner M (2000) Chromosomal imbalances in Barrett’s adenocarcinoma and the metaplasia-dysplasia-carcinoma sequence. Am J Pathol 156:555–566PubMedCrossRefGoogle Scholar
  22. 22.
    Cameron AJ, Lomboy CT, Pera M, Carpenter HA (1995) Adenocarcinoma of the esophagogastric junction and Barrett’s esophagus. Gastroenterology 109:1541–1546PubMedCrossRefGoogle Scholar
  23. 23.
    Siewert JR, Stein HJ (1996) Adenocarcinoma of the gastrointestinal junction: classification, pathology and extent of resection. Dis Esophagus 9:173–182Google Scholar
  24. 24.
    Van Dekken H, Geelen E, Dinjens WN, Wijnhoven BP, Tilanus HW, Tanke HJ, Rosenberg C (1999) 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 59:748–752PubMedGoogle Scholar
  25. 25.
    Yanagi M, Keller G, Mueller JD, Walch AK, Werner M, Stein HJ, Siewert JR, Höfler H (2000) Comparison of loss of heterozygosity and microsatellite instability in adenocarcinomas of the distal esophagus and proximal stomach. Virchows Arch (in press)Google Scholar
  26. 26.
    Nekarda H, Schlegel P, Schmitt M, Becker K, Mueller JD, Fink U (1998) Strong prognostic impact of tumor-associated urokinase-type plasminogen activator in completely resected adenocarcinoma of the esophagus. Clin Cancer Res 4: 1755–1763PubMedGoogle Scholar
  27. 27.
    Schmitt M, Harbeck N, Thomssen C, Wilhelm O, Magdolen V, Reuning U, Ulm K, Hofler H, Janicke F, Graeff H (1997) Clinical impact of the plasminogen activation system in tumor invasion and metastasis: prognostic relevance and target for therapy. Thromb Haemost 78:285–296PubMedGoogle Scholar
  28. 28.
    Natsugoe S, Mueller JD, Stein HJ, Feith M, Hofler H, Siewert JR (1998) Micrometastasis and tumor cell microinvolvement of lymph nodes in esophageal squamous cell carcinoma: frequency, associated tumor characteristics and impact on prognosis. Cancer 83:858–866PubMedCrossRefGoogle Scholar
  29. 29.
    Mueller JD, Stein HJ, Ouyang T, Natsugoe S, Feith M, Werner M, Siewert JR (2000) Frequency and clinical impact of lymph node micrometastases and tumor cell microinvolvement in adenocarcinomas of the esophagogastric junction. Cancer 89:1874–1882PubMedCrossRefGoogle Scholar
  30. 30.
    Rubio CA, Aberg B (1991) Further studies on the musculo-fibrous anomaly of the Barrett’s mucosa in esophageal carcinomas. Pathol Res Pract 187:1009–1013 188–194PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2002

Authors and Affiliations

  • James D. Mueller
    • 1
  1. 1.Chirurgische Klinik und Poliklinik, Klinikum rechts der IsarTechnische Universität MünchenMunichGermany

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