The molecular biology of esophageal adenocarcinoma

Journal of Surgical Oncology

Volumn 92, Issue 3, 2005, Pages 169-190

  Koppert, Linetta B ^a   Wijnhoven, Bas P L ^a   Van Dekken, Herman ^b   Tilanus, Hugo W ^a   Dinjens, Winand N M ^b  

^a ERASMUS MEDICAL CENTER   (Netherlands)

^b JOSEPHINE NEFKENS INSTITUTE   (Netherlands)

Author keywords

Barrett's esophagus; Esophageal adenocarcinoma; Molecular biology

Indexed keywords

CATENIN; CATHEPSIN B; CD44V6 ANTIGEN; CYCLIN B1; CYCLIN D1; CYCLIN DEPENDENT KINASE INHIBITOR 1; CYCLIN E; EPIDERMAL GROWTH FACTOR; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; FAS ANTIGEN; FIBROBLAST GROWTH FACTOR; FRAGILE HISTIDINE TRIAD PROTEIN; GEFITINIB; HEPATOCYTE NUCLEAR FACTOR 3; IMATINIB; INHIBITOR OF APOPTOSIS PROTEIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PROSTAGLANDIN; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN MDM2; SURVIVIN; TELOMERASE; TRANSFORMING GROWTH FACTOR ALPHA; TRANSFORMING GROWTH FACTOR BETA; TRASTUZUMAB; UVOMORULIN; VON HIPPEL LINDAU PROTEIN;

ANEUPLOIDY; ANTIGEN EXPRESSION; APOPTOSIS; BARRETT ESOPHAGUS; BREAST CANCER; CARCINOGENESIS; CELL PROLIFERATION; CHROMOSOME 13Q; CHROMOSOME 14Q; CHROMOSOME 17P; CHROMOSOME 18Q; CHROMOSOME 3P; CHROMOSOME 5Q; CHROMOSOME 7Q; CHROMOSOME 9P; CHROMOSOME ABERRATION; DNA CONTENT; DNA METHYLATION; DRUG TARGETING; ESOPHAGEAL ADENOCARCINOMA; ESOPHAGUS CARCINOMA; HUMAN; LEUKEMIA; LUNG CANCER; MICROSATELLITE INSTABILITY; MOLECULAR BIOLOGY; ONCOGENE RAS; PRECANCER; PRIORITY JOURNAL; PROSTAGLANDIN SYNTHESIS; PROTO ONCOGENE; REVIEW; TUMOR SUPPRESSOR GENE;

ADENOCARCINOMA; APOPTOSIS; BARRETT ESOPHAGUS; CHROMOSOME ABERRATIONS; CYCLIN D1; DNA, NEOPLASM; EPIDERMAL GROWTH FACTOR; ESOPHAGEAL NEOPLASMS; GASTROESOPHAGEAL REFLUX; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; METAPLASIA; MICROSATELLITE REPEATS; PRECANCEROUS CONDITIONS; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, ERBB-2; TUMOR SUPPRESSOR PROTEIN P53;

EID: 28844456547     PISSN: 00224790     EISSN: None     Source Type: Journal    
DOI: 10.1002/jso.20359     Document Type: Review

References (252)

1. Tselepis C, Perry I, Jankowski J: Barrett's esophagus: Disregulation of cell cycling and intercellular adhesion in the metaplasia-dysplasia-carcinoma sequence. Digestion 2000;61:1-5.
2. Cameron AJ, Ott BJ, Payne WS: The incidence of adenocarcinoma in columnar-lined (Barrett's) esophagus. N Engl J Med 1985;313:857-859.
3. Hameeteman W, Tytgat GN, Houthoff HJ, et al: Barrett's esophagus: Development of dysplasia and adenocarcinoma. Gastroenterology 1989;96:1249-1256.
4. Menke-Pluymers MB, Hop WC, Dees J, et al.: Risk factors for the development of an adenocarcinoma in columnar-lined (Barrett) esophagus. The Rotterdam Esophageal Tumor Study Group. Cancer 1993;72:1155-1158.
5. Kim R, Weissfeld JL, Reynolds JC, et al: Etiology of Barrett's metaplasia and esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev 1997;6:369-377.
6. Nowell PC: The clonal evolution of tumor cell populations. Science 1976;194:23-28.
7. Hanahan D, Weinberg RA: The hallmarks of cancer. Cell 2000;100:57-70.
8. Muyrers-Chen I, Paro R: Epigenetics: Unforeseen regulators in cancer. Biochim Biophys Acta 2001;1552:15-26.
9. Renan MJ: How many mutations are required for tumorigenesis? Implications from human cancer data. Mol Carcinog 1993;7:139-146.
10. Lengauer C, Kinzler KW, Vogelstein B: Genetic instabilities in human cancers. Nature 1998;396:643-649.
11. Modrich P, Lahue R: Mismatch repair in replication fidelity, genetic recombination, and cancer biology. Annu Rev Biochem 1996;65:101-133.
12. Riccio A, Aaltonen LA, Godwin AK, et al.: The DNA repair gene MBD4 (MED1) is mutated in human carcinomas with microsatellite instability. Nat Genet 1999;23:266-268.
13. Lynch HT, de la Chapelle A: Genetic susceptibility to non-polyposis colorectal cancer. J Med Genet 1999;36:801-818.
14. Cahill DP, Lengauer C, Yu J, et al.: Mutations of mitotic checkpoint genes in human cancers. Nature 1998;392:300-303.
15. Fodde R, Smits R, Clevers H: APC, signal transduction and genetic instability in colorectal cancer. Nat Rev Cancer 2001;1:55-67.
16. Lapidot T, Sirard C, Vormoor J, et al.: A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994;367:645-648.
17. Clarke MF: Neurobiology: At the root of brain cancer. Nature 2004;432:281-282.
18. Al-Hajj M, Wicha MS, Benito-Hernandez A, et al: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003;100:3983-3988.
19. Houghton J, Stoicov C, Nomura S, et al.: Gastric cancer originating from bone marrow-derived cells. Science 2004;306:1568-1571.
20. Marx J: Medicine. Bone marrow cells: The source of gastric cancer? Science 2004;306:1455-1457.
21. Jenkins GJ, Doak SH, Parry JM, et al.: Genetic pathways involved in the progression of Barrett's metaplasia to adenocarcinoma. Br J Surg 2002;89:824-837.
22. Wijnhoven BP, Tilanus HW, Dinjens WN: Molecular biology of Barrett's adenocarcinoma. Ann Surg 2001;233:322-337.
23. Vissers KJ, Riegman PH, Alers JC, et al.: Involvement of cancer-activating genes on chromosomes 7 and 8 in esophageal (Barrett's) and gastric cardia adenocarcinoma. Anticancer Res 2001;21:3813-3820.
24. Fitzgerald RC, Triadafilopoulos G: Recent developments in the molecular characterization of Barrett's esophagus. Dig Dis 1998;16:63-80.
25. Gibson MK, Abraham SC, Wu TT, et al: Epidermal growth factor receptor, p53 mutation, and pathological response predict survival in patients with locally advanced esophageal cancer treated with preoperative chemoradiotherapy. Clin Cancer Res 2003;9:6461-6468.
26. Paez JG, Janne PA, Lee JC, et al.: EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science 2004;304:1497-1500.
27. Dancey JE: Predictive factors for epidermal growth factor receptor inhibitors-the bull's-eye hits the arrow. Cancer Cell 2004;5:411-415.
28. Lynch TJ, Bell DW, Sordella R, et al.: Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129-2139.
29. Barber TD, Vogelstein B, Kinzler KW, et al.: Somatic mutations of EGFR in colorectal cancers and glioblastomas. N Engl J Med 2004;351:2883.
30. Jankowski J, Hopwood D, Wormsley KG: Expression of epidermal growth factor, transforming growth factor alpha, and their receptor in gastro-oesophageal diseases. Dig Dis 1993;11:1-11.
31. D'Errico A, Barozzi C, Fiorentino M, et al.: Role and new perspectives of transforming growth factor-alpha (TGF-alpha) in adenocarcinoma of the gastro-oesophageal junction. Br J Cancer 2000;82:865-870.
32. Couvelard A, Paraf F, Gratio V, et al: Angiogenesis in the neoplastic sequence of Barrett's oesophagus. Correlation with VEGF expression. J Pathol 2000;192:14-18.
33. Lord RV, Park JM, Wickramasinghe K, et al.: Vascular endothelial growth factor and basic fibroblast growth factor expression in esophageal adenocarcinoma and Barrett esophagus. J Thorac Cardiovasc Surg 2003;125:246-253.
34. Hardwick RH, Barham CP, Ozua P, et al.: Immunohistochemical detection of p53 and c-erbB-2 in oesophageal carcinoma; no correlation with prognosis. Eur J Surg Oncol 1997;23:30-35.
35. Hardwick RH, Shepherd NA, Moorghen M, et al.: c-erbB-2 overexpression in the dysplasia/carcinoma sequence of Barrett's oesophagus. J Clin Pathol 1995;48:129-132.
36. Duhaylongsod FG, Gottfried MR, Iglehart JD, et al.: The significance of c-erb B-2 and p53 immunoreactivity in patients with adenocarcinoma of the esophagus. Ann Surg 1995;221:677-683; discussion 683-674.
37. Flejou JF, Paraf F, Muzeau F, et al.: Expression of c-erbB-2 oncogene product in Barrett's adenocarcinoma: Pathological and prognostic correlations. J Clin Pathol 1994;47:23-26.
38. Polkowski W, van Sandick JW, Offerhaus GJ, et al.: Prognostic value of Lauren classification and c-erbB-2 oncogene overexpression in adenocarcinoma of the esophagus and gastroesophageal junction. Ann Surg Oncol 1999;6:290-297.
39. Nakamura T, Nekarda H, Hoelscher AH, et al.: Prognostic value of DNA ploidy and c-erbB-2 oncoprotein overexpression in adenocarcinoma of Barrett's esophagus. Cancer 1994;73:1785-1794.
40. Friess H, Fukuda A, Tang WH, et al.: Concomitant analysis of the epidermal growth factor receptor family in esophageal cancer: Overexpression of epidermal growth factor receptor mRNA but not of c-erbB-2 and c-erbB-3. World J Surg 1999;23:1010-1018.
41. Geddert H, Zeriouh M, Wolter M, et al.: Gene amplification and protein overexpression of c-erb-b2 in Barrett carcinoma and its precursor lesions. Am J Clin Pathol 2002;118:60-66.
42. Walch A, Specht K, Braselmann H, et al.: Coamplification and coexpression of GRB7 and ERBB2 is found in high grade intraepithelial neoplasia and in invasive Barrett's carcinoma. Int J Cancer 2004;112:747-753.
43. Brien TP, Odze RD, Sheehan CE, et al.: HER-2/neu gene amplification by FISH predicts poor survival in Barrett's esophagus-associated adenocarcinoma. Hum Pathol 2000;31:35-39.
44. Glick AB, Weinberg WC, Wu IH, et al.: Transforming growth factor beta 1 suppresses genomic instability independent of a G1 arrest, p53, and Rb. Cancer Res 1996;56:3645-3650.
45. Wrana JL, Attisano L, Wieser R, et al.: Mechanism of activation of the TGF-beta receptor. Nature 1994;370:341-347.
46. Souza RF, Garrigue-Antar L, Lei J, et al.: 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 1996;9:229-236.
47. Garrigue-Antar L, Souza RF, Vellucci VF, et al.: Loss of transforming growth factor-beta type II receptor gene expression in primary human esophageal cancer. Lab Invest 1996;75:263-272.
48. Tanaka S, Mori M, Mafune K, et al.: A dominant negative mutation of transforming growth factor-beta receptor type II gene in microsatellite stable oesophageal carcinoma. Br J Cancer 2000;82:1557-1560.
49. Torquati A, O'Rear L, Longobardi L, et al.: RUNX3 inhibits cell proliferation and induces apoptosis by reinstating transforming growth factor beta responsiveness in esophageal adenocarcinoma cells. Surgery 2004;136:310-316.
50. Trautmann B, Wittekind C, Strobel D, et al: K-ras point mutations are rare events in premalignant forms of Barrett's oesophagus. Eur J Gastroenterol Hepatol 1996;8:799-804.
51. Casson AG, Wilson SM, McCart JA, et al.: ras mutation and expression of the ras-regulated genes osteopontin and cathepsin L in human esophageal cancer. Int J Cancer 1997;72:739-745.
52. Arber N, Shapira I, Ratan J, et al.: Activation of c-K-ras mutations in human gastrointestinal tumors. Gastroenterology 2000;118:1045-1050.
53. Lord RV, O'Grady R, Sheehan C, et al.: K-ras codon 12 mutations in Barrett's oesophagus and adenocarcinomas of the oesophagus and oesophagogastric junction. J Gastroenterol Hepatol 2000;15:730-736.
54. Sarbia M, Arjumand J, Wolter M, et al.: Frequent c-myc amplification in high-grade dysplasia and adenocarcinoma in Barrett esophagus. Am J Clin Pathol 2001;115:835-840.
55. 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;22:305-311.
56. Lu SH, Hsieh LL, Luo FC, et al.: Amplification of the EGF receptor and c-myc genes in human esophageal cancers. Int J Cancer 1988;42:502-505.
57. van Dekken H, Geelen E, Dinjens WN, 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;59:748-752.
58. Persons DL, Croughan WS, Borelli KA, et al.: Interphase cytogenetics of esophageal adenocarcinoma and precursor lesions. Cancer Genet Cytogenet 1998;106:11-17.
59. Tselepis C, Morris CD, Wakelin D, et al.: Upregulation of the oncogene c-myc in Barrett's adenocarcinoma: Induction of c-myc by acidified bile acid in vitro. Gut 2003;52:174-180.
60. Takekura N, Yasui W, Yoshida K, et al.: pp60c-src protein kinase activity in human gastric carcinomas. Int J Cancer 1990;45:847-851.
61. Kumble S, Omary MB, Cartwright CA, et al.: Src activation in malignant and premalignant epithelia of Barrett's esophagus. Gastroenterology 1997;112:348-356.
62. Jankowski J, Coghill G, Hopwood D, et al.: Oncogenes and onco-suppressor gene in adenocarcinoma of the oesophagus. Gut 1992;33:1033-1038.
63. Buskens CJ, Ristimaki A, Offerhaus GJ, et al.: Role of cyclooxygenase-2 in the development and treatment of oesophageal adenocarcinoma. Scand J Gastroenterol Suppl 2003;23:87-93.
64. Buttar NS, Wang KK, Anderson MA, et al.: The effect of selective cyclooxygenase-2 inhibition in Barrett's esophagus epithelium: An in vitro study. J Natl Cancer Inst 2002;94:422-429.
65. Souza RF, Shewmake K, Beer DG, et al.: Selective inhibition of cyclooxygenase-2 suppresses growth and induces apoptosis in human esophageal adenocarcinoma cells. Cancer Res 2000;60:5767-5772.
66. Lagorce C, Paraf F, Vidaud D, et al.: Cyclooxygenase-2 is expressed frequently and early in Barrett's oesophagus and associated adenocarcinoma. Histopathology 2003;42:457-465.
67. Morris CD, Armstrong GR, Bigley G, et al.: Cyclooxygenase-2 expression in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. Am J Gastroenterol 2001;96:990-996.
68. Buskens CJ, Van Rees BP, Sivula A, et al.: Prognostic significance of elevated cyclooxygenase 2 expression in patients with adenocarcinoma of the esophagus. Gastroenterology 2002;122:1800-1807.
69. Kaur BS, Khamnehei N, Iravani M, et al.: Rofecoxib inhibits cyclooxygenase 2 expression and activity and reduces cell proliferation in Barrett's esophagus. Gastroenterology 2002;123:60-67.
70. Abdalla SI, Lao-Sirieix P, Novelli MR, et al.: Gastrin-induced cyclooxygenase-2 expression in Barrett's carcinogenesis. Clin Cancer Res 2004;10:4784-4792.
71. Davies H, Bignell GR, Cox C, et al.: Mutations of the BRAF gene in human cancer. Nature 2002;417:949-954.
72. Brose MS, Volpe P, Feldman M, et al.: BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res 2002;62:6997-7000.
73. Naoki K, Chen TH, Richards WG, et al.: Missense mutations of the BRAF gene in human lung adenocarcinoma. Cancer Res 2002;62:7001-7003.
74. Rajagopalan H, Bardelli A, Lengauer C, et al.: Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature 2002;418:934.
75. Sommerer F, Vieth M, Markwarth A, et al.: Mutations of BRAF and KRAS2 in the development of Barrett's adenocarcinoma. Oncogene 2004;23:554-558.
76. Fitzgerald RC: Ablative mucosectomy is the procedure of choice to prevent Barrett's cancer. Gut 2003;52:16-17.
77. Samuels Y, Wang Z, Bardelli A, et al.: High frequency of mutations of the PIK3CA gene in human cancers. Science 2004;304:554.
78. Miller CT, Moy JR, Lin L, et al.: Gene amplification in esophageal adenocarcinomas and Barrett's with high-grade dysplasia. Clin Cancer Res 2003;9:4819-4825.
79. Lin L, Miller CT, Contreras JI, et al.: The hepatocyte nuclear factor 3 alpha gene, HNF3alpha (FOXA1), on chromosome band 14q13 is amplified and overexpressed in esophageal and lung adenocarcinomas. Cancer Res 2002;62:5273-5279.
80. Zou TT, Lei J, Shi YQ, et al.: FHIT gene alterations in esophageal cancer and ulcerative colitis (UC). Oncogene 1997;15:101-105.
81. Michael D, Beer DG, Wilke CW, et al.: Frequent deletions of FHIT and FRA3B in Barrett's metaplasia and esophageal adenocarcinomas. Oncogene 1997;15:1653-1659.
82. Fang JM, Arlt MF, Burgess AC, et al.: Translocation breakpoints in FHIT and FRA3B in both homologs of chromosome 3 in an esophageal adenocarcinoma. Genes Chromosomes Cancer 2001;30:292-298.
83. Menin C, Santacatterina M, Zambon A, et al.: Anomalous transcripts and allelic deletions of the FHIT gene in human esophageal cancer. Cancer Genet Cytogenet 2000;119:56-61.
84. Albrecht B, Hausmann M, Zitzelsberger H, et al.: Array-based comparative genomic hybridization for the detection of DNA sequence copy number changes in Barrett's adenocarcinoma. J Pathol 2004;203:780-788.
85. Chen YJ, Chen PH, Lee MD, et al.: Aberrant FHIT transcripts in cancerous and corresponding non-cancerous lesions of the digestive tract. Int J Cancer 1997;72:955-958.
86. Maher ER, Kaelin WG Jr: von Hippel-Lindau disease. Medicine (Baltimore) 1997;76:381-391.
87. Vamecq J, Latruffe N: Medical significance of peroxisome proliferator-activated receptors. Lancet 1999;354:141-148.
88. Wijnhoven BP, Lindstedt EW, Abbou M, et al: Molecular genetic analysis of the von Hippel-Lindau and human peroxisome proliferator-activated receptor gamma tumor-suppressor genes in adenocarcinomas of the gastroesophageal junction. Int J Cancer 2001;94:891-895.
89. Dolan K, Garde J, Gosney J, et al.: Allelotype analysis of oesophageal adenocarcinoma: Loss of heterozygosity occurs at multiple sites. Br J Cancer 1998;78:950-957.
90. Sanz-Ortega J, Hernandez S, Saez MC, 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;50:404-407.
91. Raja S, Finkelstein SD, Baksh FK, et al.: Correlation between dysplasia and mutations of six tumor suppressor genes in Barrett's esophagus. Ann Thorac Surg 2001;72:1130-1135.
92. Dolan K, Garde J, Walker SJ, et al.: Histological and molecular mapping of adenocarcinoma of the oesophagus and gastroesophageal junction: loss of heterozygosity occurs in histologically normal epithelium in the oesophagus and stomach. Oncol Rep 2000;7:521-528.
93. Bektas N, Donner A, Wirtz C, et al.: Allelic loss involving the tumor suppressor genes APC and MCC and expression of the APC protein in the development of dysplasia and carcinoma in Barrett esophagus. Am J Clin Pathol 2000;114:890-895.
94. Zhuang Z, Vortmeyer AO, Mark EJ, et al.: Barrett's esophagus: Metaplastic cells with loss of heterozygosity at the APC gene locus are clonal precursors to invasive adenocarcinoma. Cancer Res 1996;56:1961-1964.
95. Gonzalez MV, Artimez ML, Rodrigo L, et al.: Mutation analysis of the p53, APC, and p16 genes in the Barrett's oesophagus, dysplasia, and adenocarcinoma. J Clin Pathol 1997;50:212-217.
96. Ogasawara S, Tamura G, Maesawa C, et al.: Common deleted region on the long arm of chromosome 5 in esophageal carcinoma. Gastroenterology 1996;110:52-57.
97. Powell SM, Papadopoulos N, Kanzler KW, et al.: APC gene mutations in the mutation cluster region are rare in esophageal cancers. Gastroenterology 1994;107:1759-1763.
98. Tsuchiya T, Tamura G, Sato K, et al.: Distinct methylation patterns of two APC gene promoters in normal and cancerous gastric epithelia. Oncogene 2000;19:3642-3646.
99. Kawakami K, Brabender J, Lord RV, et al.: Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma. J Natl Cancer Inst 2000;92:1805-1811.
100. Clement G, Bosman FT, Fontolliet C, et al.: Monoallelic methylation of the APC promoter is altered in normal gastric mucosa associated with neoplastic lesions. Cancer Res 2004;64:6867-6873.
101. Tarmin L, Yin J, Zhou X, et al.: Frequent loss of heterozygosity on chromosome 9 in adenocarcinoma and squamous cell carcinoma of the esophagus. Cancer Res 1994;54:6094-6096.
102. Gleeson CM, Sloan JM, McGuigan JA, et al.: Barrett's oesophagus: Microsatellite analysis provides evidence to support the proposed metaplasia-dysplasia-carcinoma sequence. Genes Chromosomes Cancer 1998;21:49-60.
103. Barrett MT, Galipeau PC, Sanchez CA, et al.: Determination of the frequency of loss of heterozygosity in esophageal adenocarcinoma by cell sorting, whole genome amplification and microsatellite polymorphisms. Oncogene 1996;12:1873-1878.
104. Nobukawa B, Abraham SC, Gill J, et al.: Clinicopathologic and molecular analysis of high-grade dysplasia and early adenocarcinoma in short- versus long-segment Barrett esophagus. Hum Pathol 2001;32:447-454.
105. Barrett MT, Sanchez CA, Prevo LJ, et al.: Evolution of neoplastic cell lineages in Barrett oesophagus. Nat Genet 1999;22:106-109.
106. Esteve A, Martel-Planche G, Sylla BS, et al.: Low frequency of p16/CDKN2 gene mutations in esophageal carcinomas. Int J Cancer 1996;66:301-304.
107. Muzeau F, Flejou JF, Thomas G, et al.: Loss of heterozygosity on chromosome 9 and p16 (MTS1, CDKN2) gene mutations in esophageal cancers. Int J Cancer 1997;72:27-30.
108. Suzuki H, Zhou X, Yin J, et al.: Intragenic mutations of CDKN2B and CDKN2A in primary human esophageal cancers. Hum Mol Genet 1995;4:1883-1887.
109. Barrett MT, Sanchez CA, Galipeau PC, et al.: Allelic loss of 9p21 and mutation of the CDKN2/p16 gene develop as early lesions during neoplastic progression in Barrett's esophagus. Oncogene 1996;13:1867-1873.
110. Klump B, Hsieh CJ, Holzmann K, et al.: Hypermethylation of the CDKN2/p16 promoter during neoplastic progression in Barrett's esophagus. Gastroenterology 1998;115:1381-1386.
111. Wong DJ, Barrett MT, Stoger R, et al.: p16INK4a promoter is hypermethylated at a high frequency in esophageal adenocarcinomas. Cancer Res 1997;57:2619-2622.
112. Wong DJ, Paulson TG, Prevo LJ, et al.: p16(TNK4a) lesions are common, early abnormalities that undergo clonal expansion in Barrett's metaplastic epithelium. Cancer Res 2001;61:8284-8289.
113. Bian YS, Osterheld MC, Fontolliet C, et al.: p16 inactivation by methylation of the CDKN2A promoter occurs early during neoplastic progression in Barrett's esophagus. Gastroenterology 2002;122:1113-1121.
114. Vieth M, Schneider-Stock R, Rohrich K, et al.: INK4a-ARF alterations in Barrett's epithelium, intraepithelial neoplasia, and Barrett's adenocarcinoma. Virchows Arch 2004;445:135-141.
115. Galipeau PC, Prevo LJ, Sanchez CA, et al.: Clonal expansion and loss of heterozygosity at chromosomes 9p and 17p in premalignant esophageal (Barrett's) tissue. J Natl Cancer Inst 1999;91:2087-2095.
116. Maley CC, Galipeau PC, Li X, et al.: Selectively advantageous mutations and hitchhikers in neoplasms: p16 lesions are selected in Barrett's esophagus. Cancer Res 2004;64:3414-3427.
117. Suspiro A, Pereira AD, Afonso A, et al.: Losses of heterozygosity on chromosomes 9p and 17p are frequent events in Barrett's metaplasia not associated with dysplasia or adenocarcinoma. Am J Gastroenterol 2003;98:728-734.
118. Sarbia M, Tekin U, Zeriouh M, et al.: Expression of the RB protein, allelic imbalance of the RB gene and amplification of the CDK4 gene in metaplasias, dysplasias and carcinomas in Barrett's oesophagus. Anticancer Res 2001;21:387-392.
119. Casson AG, Mukhopadhyay T, Cleary KR, et al.: p53 gene mutations in Barrett's epithelium and esophageal cancer. Cancer Res 1991;51:4495-4499.
120. Krishnadath KK, Tilanus HW, van Blankenstein M, et al.: Accumulation of p53 protein in normal, dysplastic, and neoplastic Barrett's oesophagus. J Pathol 1995;175:175-180.
121. Younes M, Ertan A, Lechago LV, et al.: p53 protein accumulation is a specific marker of malignant potential in Barrett's metaplasia. Dig Dis Sci 1997;42:697-701.
122. Blount PL, Meltzer SJ, Yin J, et al.: Clonal ordering of 17p and 5q allelic losses in Barrett dysplasia and adenocarcinoma. Proc Natl Acad Sci USA 1993;90:3221-3225.
123. Blount PL, Galipeau PC, Sanchez CA, et al.: 17p allelic losses in diploid cells of patients with Barrett's esophagus who develop aneuploidy. Cancer Res 1994;54:2292-2295.
124. Morgan RJ, Newcomb PV, Bailey M, et al.: Loss of heterozygosity at microsatellite marker sites for tumour suppressor genes in oesophageal adenocarcinoma. Eur J Surg Oncol 1998;24:34-37.
125. Wu TT, Watanabe T, Heitmiller R, et al.: Genetic alterations in Barrett esophagus and adenocarcinomas of the esophagus and esophagogastric junction region. Am J Pathol 1998;153:287-294.
126. Hamelin R, Flejou JF, Muzeau F, et al.: TP53 gene mutations and p53 protein immunoreactivity in malignant and premalignant Barrett's esophagus. Gastroenterology 1994;107:1012-1018.
127. Gleeson CM, Sloan JM, McGuigan JA, et al.: Base transitions at CpG dinucleotides in the p53 gene are common in esophageal adenocarcinoma. Cancer Res 1995;55:3406-3411.
128. Soslow RA, Altorki NK, Yang G, et al.: mdm-2 expression correlates with wild-type p53 status in esophageal adenocarcinoma. Mod Pathol 1999;12:580-586.
129. Neshat K, Sanchez CA, Galipeau PC, et al.: p53 mutations in Barrett's adenocarcinoma and high-grade dysplasia. Gastroenterology 1994;106:1589-1595.
130. Bian YS, Osterheld MC, Bosman FT, et al.: p53 gene mutation and protein accumulation during neoplastic progression in Barrett's esophagus. Mod Pathol 2001;14:397-403.
131. Doak SH, Jenkins GJ, Parry EM, et al.: Characterisation of p53 status at the gene, chromosomal and protein levels in oesophageal adenocarcinoma. Br J Cancer 2003;89:1729-1735.
132. Dolan K, Morris AI, Gosney JR, et al.: Loss of heterozygosity on chromosome 17p predicts neoplastic progression in Barrett's esophagus. J Gastroenterol Hepatol 2003;18:683-689.
133. Dolan K, Walker SJ, Gosney J, et al.: TP53 mutations in malignant and premalignant Barrett's esophagus. Dis Esophagus 2003;16:83-89.
134. Reid BJ, Prevo LJ, Galipeau PC, et al.: Predictors of progression in Barrett's esophagus II: Baseline 17p (p53) loss of heterozygosity identifies a patient subset at increased risk for neoplastic progression. Am J Gastroenterol 2001;96:2839-2848.
135. Schneider PM, Stoeltzing O, Roth JA, et al.: p53 mutational status improves estimation of prognosis in patients with curatively resected adenocarcinoma in Barrett's esophagus. Clin Cancer Res 2000;6:3153-3158.
136. Casson AG, Evans SC, Gillis A, et al.: 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 2003;125:1121-1131.
137. Ireland AP, Shibata DK, Chandrasoma P, et al.: Clinical significance of p53 mutations in adenocarcinoma of the esophagus and cardia. Ann Surg 2000;231:179-187.
138. Barrett MT, Schutte M, Kern SE, et al.: Allelic loss and mutational analysis of the DPC4 gene in esophageal adenocarcinoma. Cancer Res 1996;56:4351-4353.
139. Wang S, Mori Y, Sato F, et al.: An LOH and mutational investigation of the ST7 gene locus in human esophageal carcinoma. Oncogene 2003;22:467-470.
140. Sarbia M, Geddert H, Klump B, et al.: Hypermethylation of tumor suppressor genes (p16INK4A, p14ARF and APC) in adenocarcinomas of the upper gastrointestinal tract. Int J Cancer 2004;111:224-228.
141. Eads CA, Lord RV, Kurumboor SK, et al.: Fields of aberrant CpG island hypermethylation in Barrett's esophagus and associated adenocarcinoma. Cancer Res 2000;60:5021-5026.
142. Brock MV, Gou M, Akiyama Y, et al.: Prognostic importance of promoter hypermethylation of multiple genes in esophageal adenocarcinoma. Clin Cancer Res 2003;9:2912-2919.
143. Eads CA, Lord RV, Wickramasinghe K, et al.: Epigenetic patterns in the progression of esophageal adenocarcinoma. Cancer Res 2001;61:3410-3418.
144. Meltzer SJ, Yin J, Manin B, et al.: Microsatellite instability occurs frequently and in both diploid and aneuploid cell populations of Barrett's-associated esophageal adenocarcinomas. Cancer Res 1994;54:3379-3382.
145. Keller G, Rotter M, Vogelsang H, et al.: Microsatellite instability in adenocarcinomas of the upper gastrointestinal tract. Relation to clinicopathological data and family history. Am J Pathol 1995;147:593-600.
146. Kulke MH, Thakore KS, Thomas G, et al.: Microsatellite instability and hMLH1/hMSH2 expression in Barrett esophagus-associated adenocarcinoma. Cancer 2001;91:1451-1457.
147. Evans SC, Gillis A, Geldenhuys L, et al.: Microsatellite instability in esophageal adenocarcinoma. Cancer Lett 2004;212:241-251.
148. Orr-Weaver TL, Weinberg RA: A checkpoint on the road to cancer. Nature 1998;392:223-224.
149. Mogensen MM, Tucker JB, Mackie JB, et al.: The adenomatous polyposis coli protein unambiguously localizes to microtubule plus ends and is involved in establishing parallel arrays of microtubule bundles in highly polarized epithelial cells. J Cell Biol 2002;157:1041-1048.
150. Doak SH, Jenkins GJ, Parry EM, et al.: Differential expression of the MAD2, BUB1, and HSP27 genes in Barrett's oesophagus-their association with aneuploidy and neoplastic progression. Mutat Res 2004;547:133-144.
151. Zumbrunn J, Kinoshita K, Hyman AA, et al.: Binding of the adenomatous polyposis coli protein to microtubules increases microtubule stability and is regulated by GSK3 beta phosphorylation. Curr Biol 2001;11:44-49.
152. Levine DS, Reid BJ, Haggitt RC, et al.: Correlation of ultrastructural aberrations with dysplasia and flow cytometric abnormalities in Barrett's epithelium. Gastroenterology 1989;96:355-367.
153. Reid BJ, Blount PL, Rubin CE, et al.: Flow-cytometric and histological progression to malignancy in Barrett's esophagus: Prospective endoscopic surveillance of a cohort. Gastroenterology 1992;102:1212-1219.
154. Reid BJ, Haggitt RC, Rubin CE, et al.: Barrett's esophagus. Correlation between flow cytometry and histology in detection of patients at risk for adenocarcinoma. Gastroenterology 1987;93:1-11.
155. Reid BJ, Levine DS, Longton G, et al.: Predictors of progression to cancer in Barrett's esophagus: Baseline histology and flow cytometry identify low- and high-risk patient subsets. Am J Gastroenterol 2000;95:1669-1676.
156. Fang M, Lew E, Klein M. et al.: DNA abnormalities as marker of risk for progression of Barrett's esophagus to adenocarcinoma: Image cytometric DNA analysis in formalin-fixed tissues. Am J Gastroenterol 2004;99:1887-1894.
157. Teodori L, Gohde W, Persiani M, et al.: DNA/protein flow cytometry as a predictive marker of malignancy in dysplasia-free Barrett's esophagus: Thirteen-year follow-up study on a cohort of patients. Cytometry 1998;34:257-263.
158. James PD, Atkinson M: Value of DNA image cytometry in the prediction of malignant change in Barrett's oesophagus. Gut 1989;30:899-905.
159. Rabinovitch PS, Longton G, Blount PL, et al.: Predictors of progression in Barrett's esophagus III: Baseline flow cytometric variables. Am J Gastroenterol 2001;96:3071-3083.
160. Rodriguez E, Mathew S, Reuter V, et al.: Cytogenetic analysis of 124 prospectively ascertained male germ cell tumors. Cancer Res 1992;52:2285-2291.
161. Raskind WH, Norwood T, Levine DS, et al.: Persistent clonal areas and clonal expansion in Barrett's esophagus. Cancer Res 1992;52:2946-2950.
162. Garewal HS, Sampliner R, Liu Y, et al: Chromosomal rearrangements in Barrett's esophagus. A premalignant lesion of esophageal adenocarcinoma. Cancer Genet Cytogenet 1989;42:281-286.
163. Menke-Pluymers MB, van Drunen E, Vissers KJ, et al.: Cytogenetic analysis of Barrett's mucosa and adenocarcinoma of the distal esophagus and cardia. Cancer Genet Cytogenet 1996;90:109-117.
164. Doak SH, Jenkins GJ, Parry EM, et al.: Chromosome 4 hyperploidy represents an early genetic aberration in premalignant Barrett's oesophagus. Gut 2003;52:623-628.
165. Croft J, Parry EM, Jenkins GJ, et al.: Analysis of the premalignant stages of Barrett's oesophagus through to adenocarcinoma by comparative genomic hybridization. Eur J Gastroenterol Hepatol 2002;14:1179-1186.
166. Walch AK, Zitzelsberger HF, Bruch J, et al.: Chromosomal imbalances in Barrett's adenocarcinoma and the metaplasia-dysplasia-carcinoma sequence. Am J Pathol 2000;156:555-566.
167. Riegman PH, Vissers KJ, Alers JC, et al.: Genomic alterations in malignant transformation of Barrett's esophagus. Cancer Res 2001;61:3164-3170.
168. Dolan K, Garde J, Walker SJ, et al.: LOH at the sites of the DCC, APC, and TP53 tumor suppressor genes occurs in Barrett's metaplasia and dysplasia adjacent to adenocarcinoma of the esophagus. Hum Pathol 1999;30:1508-1514.
169. El-Rifai W, Frierson HF Jr, Moskaluk CA, et al.: Genetic differences between adenocarcinomas arising in Barrett's esophagus and gastric mucosa. Gastroenterology 2001;121:592-598.
170. El-Rifai W, Harper JC, Cummings OW, et al.: Consistent genetic alterations in xenografts of proximal stomach and gastroesophageal junction adenocarcinomas. Cancer Res 1998;58:34-37.
171. van Dekken H, Alers JC, Riegman PH, et al.: Molecular cytogenetic evaluation of gastric cardia adenocarcinoma and precursor lesions. Am J Pathol 2001;158:1961-1967.
172. Huang Y, Boynton RF, Blount PL, et al.: Loss of heterozygosity involves multiple tumor suppressor genes in human esophageal cancers. Cancer Res 1992;52:6525-6530.
173. Krishnadath KK, Tilanus HW, Alers JC, et al.: Detection of genetic changes in Barrett's adenocarcinoma and Barrett's esophagus by DNA in situ hybridization and immunohistochemistry. Cytometry 1994;15:176-184.
174. Varis A, Puolakkainen P, Savolainen H, et al.: DNA copy number profiling in esophageal Barrett adenocarcinoma: Comparison with gastric adenocarcinoma and esophageal squamous cell carcinoma. Cancer Genet Cytogenet 2001;127:53-58.
175. Beuzen F, Dubois S, Flejou JF: Chromosomal numerical aberrations are frequent in oesophageal and gastric adenocarcinomas: A study using in-situ hybridization. Histopathology 2000;37:241-249.
176. Walch AK, Zitzelsberger HF, Bink K, et al.: Molecular genetic changes in metastatic primary Barrett's adenocarcinoma and related lymph node metastases: Comparison with nonmetastatic Barrett's adenocarcinoma. Mod Pathol 2000;13:814-824.
177. Sinicrope FA, Roddey G, McDonnell TJ, et al.: Increased apoptosis accompanies neoplastic development in the human colorectum. Clin Cancer Res 1996;2:1999-2006.
178. Soslow RA, Remotti H, Baergen RN, et al.: Suppression of apoptosis does not foster neoplastic growth in Barrett's esophagus. Mod Pathol 1999;12:239-250.
179. Whittles CE, Biddlestone LR, Burton A, et al.: Apoptotic and proliferative activity in the neoplastic progression of Barrett's oesophagus: A comparative study. J Pathol 1999;187:535-540.
180. Gillen P, McDermott M, Grehan D, et al.: Proliferating cell nuclear antigen in the assessment of Barrett's mucosa. Br J Surg 1994;81:1766-1768.
181. Kimos MC, Wang S, Borkowski A, et al.: Esophagin and proliferating cell nuclear antigen (PCNA) are biomarkers of human esophageal neoplastic progression. Int J Cancer 2004;111:415-417.
182. Lauwers GY, Kandemir O, Kubilis PS, et al.: Cellular kinetics in Barrett's epithelium carcinogenic sequence: Roles of apoptosis, bcl-2 protein, and cellular proliferation. Mod Pathol 1997;10:1201-1208.
183. Jankowski J, McMenemin R, Yu C, et al.: Proliferating cell nuclear antigen in oesophageal diseases; correlation with transforming growth factor alpha expression. Gut 1992;33:587-591.
184. Hong MK, Laskin WB, Herman BE, et al.: Expansion of the Ki67 proliferative compartment correlates with degree of dysplasia in Barrett's esophagus. Cancer 1995;75:423-429.
185. Polkowski W, van Lanschot JJ, Ten Kate FJ, et al.: The value of p53 and Ki67 as markers for tumour progression in the Barrett's dysplasia-carcinoma sequence. Surg Oncol 1995;4:163-171.
186. Yacoub L, Goldman H, Odze RD: Transforming growth factor-alpha, epidermal growth factor receptor, and MiB-1 expression in Barrett's-associated neoplasia: Correlation with prognosis. Mod Pathol 1997;10:105-112.
187. Rioux-Leclercq N, Turlin B, Sutherland F, et al.: Analysis of Ki-67, p53 and Bcl-2 expression in the dysplasia-carcinoma sequence of Barrett's esophagus. Oncol Rep 1999;6:877-882.
188. Krishnadath KK, Tilanus HW, van Blankenstein M, et al: Accumulation of genetic abnormalities during neoplastic progression in Barrett's esophagus. Cancer Res 1995;55:1971-1976.
189. Halm U, Tannapfel A, Breitung B, et al.: Apoptosis and cell proliferation in the metaplasia-dysplasia-carcinoma-sequence of Barrett's esophagus. Hepatogastroenterology 2000;47:962-966.
190. Going JJ, Keith WN, Neilson L, et al.: Aberrant expression of minichromosome maintenance proteins 2 and 5, and Ki-67 in dysplastic squamous oesophageal epithelium and Barrett's mucosa. Gut 2002;50:373-377.
191. Ouatu-Lascar R, Fitzgerald RC, Triadafilopoulos G: Differentiation and proliferation in Barrett's esophagus and the effects of acid suppression. Gastroenterology 1999;117:327-335.
192. Wetscher GJ, Schwelberger H, Unger A, et al.: Reflux-induced apoptosis of the esophageal mucosa is inhibited in Barrett's epithelium. Am J Surg 1998;176:569-573.
193. Katada N, Hinder RA, Smyrk TC, et al.: Apoptosis is inhibited early in the dysplasia-carcinoma sequence of Barrett esophagus. Arch Surg 1997;132:728-733.
194. Hughes SJ, Nambu Y, Soldes OS, et al.: Fas/APO-1 (CD95) is not translocated to the cell membrane in esophageal adenocarcinoma. Cancer Res 1997;57:5571-5578.
195. Younes M, Schwartz MR, Finnie D, et al.: Overexpression of Fas ligand (FasL) during malignant transformation in the large bowel and in Barrett's metaplasia of the esophagus. Hum Pathol 1999;30:1309-1313.
196. Younes M, Lechago J, Ertan A, et al.: Decreased expression of Fas (CD95/APO1) associated with goblet cell metaplasia in Barrett's esophagus. Hum Pathol 2000;31:434-438.
197. Reed JC: Bcl-2 and the regulation of programmed cell death. J Cell Biol 1994;124:1-6.
198. Goldblum JR, Rice TW: bcl-2 protein expression in the Barrett's metaplasia-dysplasia-carcinoma sequence. Mod Pathol 1995;8:866-869.
199. Beardsmore DM, Verbeke CS, Davies CL, et al.: Apoptotic and proliferative indexes in esophageal cancer: Predictors of response to neoadjuvant therapy [corrected]. J Gastrointest Surg 2003;7:77-86; discussion 86-77.
200. van der Woude CJ, Jansen PL, Tiebosch AT, et al.: Expression of apoptosis-related proteins in Barrett's metaplasia-dysplasia-carcinoma sequence: A switch to a more resistant phenotype. Hum Pathol 2002;33:686-692.
201. Chatelain D, Flejou JF: High-grade dysplasia and superficial adenocarcinoma in Barrett's esophagus: Histological mapping and expression of p53, p21 and Bcl-2 oncoproteins. Virchows Arch 2003;442:18-24.
202. Iravani S, Zhang HQ, Yuan ZQ, et al.: Modification of insulin-like growth factor 1 receptor, c-Src, and Bcl-XL protein expression during the progression of Barrett's neoplasia. Hum Pathol 2003;34:975-982.
203. Raouf AA, Evoy DA, Carton E, et al.: Loss of Bcl-2 expression in Barrett's dysplasia and adenocarcinoma is associated with tumor progression and worse survival but not with response to neoadjuvant chemoradiation. Dis Esophagus 2003;16:17-23.
204. Bond GL, Hu W, Bond EE, et al.: A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell 2004;119:591-602.
205. Li F, Ambrosini G, Chu EY, et al.: Control of apoptosis and mitotic spindle checkpoint by survivin. Nature 1998;396:580-584.
206. Kawasaki H, Altieri DC, Lu CD, et al.: Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Res 1998;58:5071-5074.
207. Sarela AI, Macadam RC, Farmery SM, et al.: Expression of the antiapoptosis gene, survivin, predicts death from recurrent colorectal carcinoma. Gut 2000;46:645-650.
208. Adida C, Berrebi D, Peuchmaur M, et al.: Anti-apoptosis gene, survivin, and prognosis of neuroblastoma. Lancet 1998;351:882-883.
209. Swana HS, Grossman D, Anthony JN, et al.: Tumor content of the antiapoptosis molecule survivin and recurrence of bladder cancer. N Engl J Med 1999;341:452-453.
210. Nemoto T, Kitagawa M, Hasegawa M, et al.: Expression of IAP family proteins in esophageal cancer. Exp Mol Pathol 2004;76:253-259.
211. Lord RV, Salonga D, Danenberg KD, et al.: Telomerase reverse transcriptase expression is increased early in the Barrett's metaplasia, dysplasia, adenocarcinoma sequence. J Gastrointest Surg 2000;4:135-142.
212. Morales CP, Lee EL, Shay JW: In situ hybridization for the detection of telomerase RNA in the progression from Barrett's esophagus to esophageal adenocarcinoma. Cancer 1998;83:652-659.
213. Reid BJ, Sanchez CA, Blount PL, et al.: Barrett's esophagus: Cell cycle abnormalities in advancing stages of neoplastic progression. Gastroenterology 1993;105:119-129.
214. Roncalli M, Bosari S, Marchetti A, et al.: Cell cycle-related gene abnormalities and product expression in esophageal carcinoma. Lab Invest 1998;78:1049-1057.
215. Arber N, Lightdale C, Rotterdam H, et al.: Increased expression of the cyclin D1 gene in Barrett's esophagus. Cancer Epidemiol Biomarkers Prev 1996;5:457-459.
216. Arber N, Gammon MD, Hibshoosh H, et al.: Overexpression of cyclin D1 occurs in both squamous carcinomas and adenocarcinomas of the esophagus and in adenocarcinomas of the stomach. Hum Pathol 1999;30:1087-1092.
217. Kuwahara M, Hirai T, Yoshida K, et al.: p53, p21(Waf1/Cip1) and cyclin D1 protein expression and prognosis in esophageal cancer. Dis Esophagus 1999;12:116-119.
218. Morgan RJ, Newcomb PV, Hardwick RH, et al.: Amplification of cyclin D1 and MDM-2 in oesophageal carcinoma. Eur J Surg Oncol 1999;25:364-367.
219. Shimada Y, Imamura M, Shibagaki I, et al.: Genetic alterations in patients with esophageal cancer with short- and long-term survival rates after curative esophagectomy. Ann Surg 1997;226:162-168.
220. Bani-Hani K, Martin IG, Hardie LJ, et al.: Prospective study of cyclin D1 overexpression in Barrett's esophagus: Association with increased risk of adenocarcinoma. J Natl Cancer Inst 2000;92:1316-1321.
221. Geddert H, Heep HJ, Gabbert HE, et al.: Expression of cyclin B1 in the metaplasia-dysplasia-carcinoma sequence of Barrett esophagus. Cancer 2002;94:212-218.
222. Sarbia M, Bektas N, Muller W, et al: Expression of cyclin E in dysplasia, carcinoma, and nonmalignant lesions of Barrett esophagus. Cancer 1999;86:2597-2601.
223. Lin L, Aggarwal S, Glover TW, et al.: A minimal critical region of the 8p22-23 amplicon in esophageal adenocarcinomas defined using sequence tagged site-amplification mapping and quantitative polymerase chain reaction includes the GATA-4 gene. Cancer Res 2000;60:1341-1347.
224. Hanas JS, Lerner MR, Lightfoot SA, et al.: Expression of the cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) and p53 tumor suppressor in dysplastic progression and adenocarcinoma in Barrett esophagus. Cancer 1999;86:756-763.
225. Moskaluk CA, Heitmiller R, Zahurak M, et al: p53 and p21 (WAF1/CIP1/SDI1) gene products in Barrett esophagus and adenocarcinoma of the esophagus and esophagogastric junction. Hum Pathol 1996;27:1211-1220.
226. Singh SP, Lipman J, Goldman H, et al.: Loss or altered subcellular localization of p27 in Barrett's associated adenocarcinoma. Cancer Res 1998;58:1730-1735.
227. Bailey T, Biddlestone L, Shepherd N, et al.: Altered cadherin and catenin complexes in the Barrett's esophagus-dysplasia-adenocarcinoma sequence: Correlation with disease progression and dedifferentiation. Am J Pathol 1998;152:135-144.
228. Krishnadath KK, Tilanus HW, van Blankenstein M, et al.: Reduced expression of the cadherin-catenin complex in oesophageal adenocarcinoma correlates with poor prognosis. J Pathol 1997;182:331-338.
229. Wijnhoven BP, de Both NJ, van Dekken H, et al.: E-cadherin gene mutations are rare in adenocarcinomas of the oesophagus. Br J Cancer 1999;80:1652-1657.
230. Corn PG, Heath EI, Heitmiller R, et al.: Frequent hypermethylation of the 5' CpG island of E-cadherin in esophageal adenocarcinoma. Clin Cancer Res 2001;7:2765-2769.
231. Morin PJ: beta-catenin signaling and cancer. Bioessays 1999;21:1021-1030,
232. Kikuchi A: Regulation of beta-catenin signaling in the Wnt pathway. Biochem Biophys Res Commun 2000;268:243-248.
233. Osterheld MC, Bian YS, Bosman FT, et al.: Beta-catenin expression and its association with prognostic factors in adenocarcinoma developed in Barrett esophagus. Am J Clin Pathol 2002;117:451-456.
234. Choi YW, Heath EI, Heitmiller R, et al.: Mutations in beta-catenin and APC genes are uncommon in esophageal and esophagogastric junction adenocarcinomas. Mod Pathol 2000;13:1055-1059.
235. Bian YS, Osterheld MC, Bosman FT, et al.: Nuclear accumulation of beta-catenin is a common and early event during neoplastic progression of Barrett esophagus. Am J Clin Pathol 2000;114:583-590.
236. Wijnhoven BP, Nollet F, De Both NJ, et al.: Genetic alterations involving exon 3 of the beta-catenin gene do not play a role in adenocarcinomas of the esophagus. Int J Cancer 2000;86:533-537.
237. Wielenga VJ, Smits R, Korinek V, et al.: Expression of CD44 in Ape and Tcf mutant mice implies regulation by the WNT pathway. Am J Pathol 1999;154:515-523.
238. Bottger TC, Youssef V, Dutkowski P, et al.: Expression of CD44 variant proteins in adenocarcinoma of Barrett's esophagus and its relation to prognosis. Cancer 1998;83:1074-1080.
239. Lagorce-Pages C, Paraf F, Dubois S, et al.: Expression of CD44 in premalignant and malignant Barrett's oesophagus. Histopathology 1998;32:7-14.
240. Menges M, Goebel R, Pueschel W, et al.: Expression of CD44v5 and -v6 in Barrett's carcinoma is not increased compared to that in nondysplastic Barrett's mucosa. Exp Mol Pathol 2002;72:207-212.
241. Keppler D, Sameni M, Moin K, et al.: Tumor progression and angiogenesis: Cathepsin B & Co. Biochem Cell Biol 1996;74:799-810.
242. Weir B, Zhao X, Meyerson M: Somatic alterations in the human cancer genome. Cancer Cell 2004;6:433-438.
243. Brabender J, Marjoram P, Salonga D, et al.: A multigene expression panel for the molecular diagnosis of Barrett's esophagus and Barrett's adenocarcinoma of the esophagus. Oncogene 2004;23:4780-4788.
244. Dahlberg PS, Ferrin LF, Grindle SM, et al.: Gene expression profiles in esophageal adenocarcinoma. Ann Thorac Surg 2004;77:1008-1015.
245. Hourihan RN, O'Sullivan GC, Morgan JG: Transcriptional gene expression profiles of oesophageal adenocarcinoma and normal oesophageal tissues. Anticancer Res 2003;23:161-165.
246. Owonikoko T, Rees M, Gabbert HE, et al.: Intratumoral genetic heterogeneity in Barrett adenocarcinoma. Am J Clin Pathol 2002;117:558-566.
247. Prevo LJ, Sanchez CA, Galipeau PC, et al.: p53-mutant clones and field effects in Barrett's esophagus. Cancer Res 1999;59:4784-4787.
248. Maley CC, Galipeau PC, Li X, et al.: The combination of genetic instability and clonal expansion predicts progression to esophageal adenocarcinoma. Cancer Res 2004;64:7629-7633.
249. van Dekken H, Vissers CJ, Tilanus HW, et al.: Clonal analysis of a case of multifocal oesophageal (Barrett's) adenocarcinoma by comparative genomic hybridization. J Pathol 1999;188:263-266.
250. Gleeson CM, Sloan JM, McGuigan JA, et al.: Ubiquitous somatic alterations at microsatellite alleles occur infrequently in Barrett's-associated esophageal adenocarcinoma. Cancer Res 1996;56:259-263.
251. Muzeau F, Flejou JF, Belghiti J, et al.: Infrequent microsatellite instability in oesophageal cancers. Br J Cancer 1997;75:1336-1339.
252. Falkenback D, Johansson J, Halvarsson B, et al.: Defective mismatch-repair as a minor tumorigenic pathway in Barrett esophagus-associated adenocarcinoma. Cancer Genet Cytogenet 2005;157:82-86.