Abstract
The risk of developing gastroesophagealadenocarcinoma is increased in patients with Barrett'sesophagus. The management of dysplasia in Barrett'sesophagus remains controversial. Understanding of thesequence of events preceding malignancy is essentialbefore screening protocols for early diagnosis andpreventive measures can be implemented. The aim of thisreview is to examine the published data on the role p53 assessment may play in the management ofBarrett's esophagus. Relevant papers were identified byan extensive text word search of the Medline databaseand a review of quoted articles. The p53 abnormality occurs more frequently in highly dysplasticepithelium than in nondysplastic epithelium. However,the retrospective nature of most of the available datacould be a significant confounding factor. Our current knowledge suggests that p53 proteinoverexpression does not seem to predict futureprogression to cancer or determine disease outcome. Thep53 abnormality alone can not be reliably used topredict progression of Barrett's esophagus to cancer. We must awaitlong-term evaluation of patients to determine thepercentage of patients with p53 gene abnormality, andnondysplastic Barrett's who will progress to dysplasia or carcinoma. Large randomized controlledlong-term follow-up studies are much needed.
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REFERENCES
Blot WJ, Devesa SS, Kneller RW, et al: Rising incidenceof adenocarcinoma of theesophagus and gastric cardia. JAMA 265:1287–1289, 1991
Haggitt RC: Adenocarcinoma in Barrett' s oesophagus: a new epidemic? Human Pathol 23:475–6, 1992
Clark GWB, Ireland AP, De Meester TR: Dysplasia in Barrett's oesophagus: Diagnosis, surveillance and treatment. Dig Dis 14:213–227, 1996
Jones DR, Davidson AG, Summers CL, et al: Potential application of p53 as an intermediate biomarker in Barrett's oesophagus. Ann Thorac Surg 57:598–603, 1994
Naef AP, Savary M, Ozzello L, Pearson FG: Columnar lined lower oesophagus. An acquired lesion with malignant predisposition. Report of 140 cases of Barrett's oesophagus with 12 adenocarcinomas. Ann Thorac Surg 13:543–551, 1972
Barrett N: Chronic peptic ulcer of the oesophagus and oesophagitis. Br J Surg 38:175–82, 1950
Spechler SJ, Robbins AH, Rubins HB, et al: Adenocarcinoma and Barrett's oesophagus. Gastroenterology 87:927–933, 1984
Jaskiewicz K, Louw J, Anichkov N: Barrett's oesophagus: Mucin composition, neuroendocrine cells, cellular proliferation and differentiation. Anticancer Res 14:1907–1912, 1994
Overholt B, Panjehpour M, Tefftellar E, Rose M: PDT for treatment of early adenocarcinoma in Barrett's oesophagus. Gastrointest Endosc 39:73–76, 1993
Reid BJ, Blount PL, Rubin CE, et al: Flow cytometric and histological progression to malignancy in Barrett's oesophagus: Prospective endoscopic surveillance of a cohort. Gastroenterology 102:1212–1219, 1992
Polkowski W, Van Lanschot JJB, Tenkate FJW, et al: The valueof p53 and Ki67 as markers for tumour progression in the Barrett's dysplasia- carcinoma sequence. Surg Oncol 4:163–171, 1995
Altorki NK, Sunagawa M, Little AG, Skinner DB: High grade dysplasia in the columnar lined oesophagus. Am J Surg 161:97–99, 1991
Schnell T, Sontag S, Chejfec G, et al: High grade dysplasia in Barrett's oesophagus: A report of experience with 43 patients. Gastroenterology 96:A452, 1989
Younes M, Lebovitz RM, Lechago LV, et al: p53 protein accumulation in Barrett's metaplasia, dysplasia and carcinoma: A follow-up study. Gastroenterology 105:1637–42, 1993
Wright TA, Gray MR, Morris AI, et al: Cost effectiveness of detecting Barrett's cancer. Gut 39(4):574–9, 1996
Achkar E, Carey W: Thecost for surveillance of adenocarcinoma complicating Barrett's esophagus. Am J Gastroenterol 83:291–294, 1988
McKinley MJ, Budman DR, Gruenberg D, et al: DNA content in Barrett's oesophagus and esophageal malignancy. Am J Gastroenterol 82:1012–1015, 1987
Krishnadath KK, Tilanus HW, van Blankenstein M, Hop WC, Teijgeman R, Mulder AH, Bosman FT, van Dekken: Accumulation of genetic abnormalities during neoplastic progression in Burret's esophagus. Cancer Research 55:1971–1976, 1995
Ohgaki H, Hard GC, Hirota N, et al: Selective mutation of codens 204 and 213 of thep53 gene in rat tumours induced by alkylating N-nitrosocompounds. Cancer Res 52:2995–2998, 1992
Jankowski J, Jonkowski RF, Wormsley KG: Oesophageal carcinoma: The need for screening. Eur J Cancer Prev 3:5–15, 1993
Nowell PC: Theclonal evolution of tumour cell populations. Science 194:23–28, 1976
Lane DP, Crawford LV: T antigen is bound to a host protein in SV 40 transformed cells. Nature 278:261–263, 1979
Isobe M, Emanuel BS, Givol D: Localisation of gene for human p53 tumour antigen to band 17p13. Nature 320:84–85, 1986
Tjian R: Molecular machines that control genes. Sci Am 00:54–61, 1995
Fazeli A, Steen RG, Dickinson SL, et al: Effects of p53 mutations on apoptosis in mouse intestinal and human colonic adenomas. Proc Natl Acad Sci USA 94:10199–10204, 1997
Blount PL, Galipeau PC, Sanchez CA, et al: p53 is frequently mutated in Barrett's metaplasia of the intestinal type. Cancer Epidemiol Biomarkers Prev 5:559–565, 1996
Roth JA: The cell and molecular biology of oesophageal carcinoma. Chest Surg Clin North Am 4(2):205–216, 1994
Levine AJ: Tumour suppressor genes. Bioassays 12:60–66, 1990
Krishnadath KK, Van Blankenstein M, Tilanus W: Prognostic valueof p53 in Barrett' s oesophagus. Eur J Gastroenterol Hepatol 7:81–84, 1995
Oren M, Maltzman W, Levine AJ: Posttranslational regulation of the 54K cellular tumour antigen in normal and transformed cells. Mol Cell Biol 1:101–110, 1981
Levine DS: Barrett' s oesophagus and p53. Lancet 344:212–213, 1994
Greenblatt MS, Bennett WP, Hollstein MC, Harris CC: Mutations in thep53 tumor suppressor gene: Clues to cancer aetiology and molecular pathogenesis. Cancer Res 54:2995–2998, 1994
Iggo R, Gatter K, Bartek J, et al: Increased expression of mutant forms of p53 oncogenein primary lung cancer. Lancet 335:675–679, 1990
Laurent-Puig P, Flejou J-F, Fabre M, et al: Overexpression of p53: A rare event in a large series of white patients with hepatocellular carcinomas. Hepatology 16:1171–5, 1992
Jankowski J, Coghill G, Hopwood D, et al: Oncogenes and oncosuppressor genes in adenocarcinoma or the oesophagus. Gut 32:A1205–6, 1991
Filipe MI, Jankowski J: Growth factors and oncogenes in Barrett's oesophagus and gastric metaplasia. Endoscopy 25( suppl):637–641, 1993
Wagata T, Shibagaki I, Imamura M, et al: Loss of 17p, mutation of thep53 gene and overexpression of p53 protein in oesophageal squamous cell carcinomas. Cancer Res 53:846–50, 1993
Casson AG, Mukhopadhyay T, Cleary KR, et al: p53 gene mutation in Barrett' s epithelium and oesophageal cancer. Cancer Res 51:4495–9, 1991
Blount PI, Ramel S, Raskind WH, et al. 17p allelic deletions and p53 protein over-expression in Barrett' s adenocarcinoma. Cancer Res 51:5482–6, 1991
Wyndford-Thomas D: p53 in tumour pathology: Can wetrust immunocytochemistry? J Pathol 166:329–330, 1992
Levine AJ, Momand J, Finlay CA: The p53 tumour suppressor gene. Nature 351:453–456, 1991
Krishnadath KK, Tilanus HW, Van Blankstein M, et al: Accumulation pf p53 protein in normal, dysplastic and neoplastic Barrett's oesophagus. J Pathol 175:175–180, 1995
Malkin D, Li FP, Strong LC, et al: Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas and other neoplasms. Science 250:1233–1238, 1990
Rice TW, Goldblum JR, Falk GW, et al: p53 immunoreactivity in Barrett' s metaplasia, dysplasia and carcinoma. J Thorac Cardiovasc Surg 108:1132–7, 1994
Lu X, Park SH, Thompson TC, Lane DP: Ras-induced hyperplasia occurs with mutation of p53 but activated ras and myc together can induce carcinoma without p53 mutation. Cell 70:153–161, 1992
Greenblatt MS, Bennett WP, Hollstein MC, Harris CC: Mutations in thep53 tumour suppressor gene: Clues to cancer aetiology and molecular pathogenesis. Cancer Res 54:4855–4878, 1994
Ramel S, Reid BJ, Sanchez CA, et al: Evaluation of p53 protein expression in Barrett' s oesophagus by two parameter flow cytometry. Gastroenterology 102:1220–1228, 1992
Rodriques NR, Rowan A, Smith MEF, et al: p53 mutations in colorectal cancer. Proc Natl Acad Sci USA 87:7555–7559, 1990
Baetek J, Bartkova J, Vojtesek B, et al: Patterns of theexpression of thep53 tumour suppressor in human breast tissues and tumours in situ and in vitro. Int J Cancer 46:839–844, 1990
Flejou JF, Muzeau F, Potet F, et al: Overexpression of thep53 tumour suppressor gene product in oesophageal and gastric carcinomas. Pathol Res Pract 190:1141–1148, 1994
Flejou JF, Potet F, Muzeau F, et al: Overexpression of p53 protein in Barrett's syndrome with malignant transformation. Clin Pathol 46:330–333, 1993
Flejou JF, Paraf F, Potet F, et al: p53 protein expression in Barrett's adenocarcinoma: A frequent event with no prognostic significance. Histopathology 24:487–489, 1994
Symmans PJ, Linehan JM, Brito MJ, Filipe MI: p53 expression in Barrett's oesophagus, dysplasia and adenocarcinoma using antibody DO-7. J Pathol 173:221–226, 1994
Roth JA: Molecular surgery for cancer. Arch Surg 127:1298–1302, 1992
Campomenosi P, Conio M, Bogliolo M, et al: p53 is frequently mutated in Barrett's metaplasia of the intestinal type. Cancer Epidemiol Biomarkers Prev 5:559–565, 1996
Neshat K, Sanchez CA, Galipeau PC, et al: p53 mutations in Barrett's adenocarcinoma and high grade dysplasia. Gastroenterology 106:1589–1595, 1994
Li AGK, Gaunt M, Reynolds JV, et al: p53 immunohistochemistry identifies at risk patients with Barrett's oesophagus. The Surgical Research Society 10th Tripartitemeeting, Nottingham, July 1997, Abstract 129
Gleeson CM, Sloan JM, McGuigan JA, et al: Base transitions at CpG dinucleotidein thep53 genearecommon in oesophage al adenocarcinoma. Cancer Res 55:3406–3411, 1995
Wang Y, You M, Reynolds SH, et al: Mutational activation of the cellular harvey ras oncogenein rat esophageal pappilomas induced by methyl benzylnitrosamine. Cancer Res 50:1591–1595, 1990
Swift A, Risk JM, Kingsnorth AN, Wright TA, et al: Frequent loss of heterozygosity on chromosome17 at 17q11.2-q12 in Barrett's adenocarcinoma. Br J Cancer 71:995–998, 1995
Galipeau PC, Cowan DS, Sanchez CA, et al: 17p (p53) allelic losses, 4N (G2/tetraploid) populations and progression to aneuploidy in Barrett' s oesophagus. J Natl Acad Sci 93:7081–7084, 1996
Reid BJ: Barrett' s esophagus and esophageal adenocarcinoma. Gastroenterol Clin North Am 20:817–834, 1991
Blount PL, Meltzer SJ, Yin J, et al: Clonal ordering of 17p and 5q allelic losses in Barrett's dysplasia and adenocarcinoma. Proc Natl Acad Sci USA 90:3221–3225, 1993
Blount PL, Galipeau PC, Sanchez CA, Neshat K, et al: 17p allelic losses in diploid cells of patients with Barretts oesophagus who develop aneuploidy. Cancer Res 54:2292–2295, 1994
Jankowski J, Coghill G, Hopwood D, Wormsley KG: Oncogenes and onco-suppressor gene in adenocarcinoma of the oesophagus. Gut 33:1033–1038, 1992
Moore JH, Lesser EJ, Erdody DH, et al: Intestinal differentiation and p53 gene alterations in Barrett' s oesophagus and oesophageal adenocarcinoma. Int J Cancer 56:487–493, 1994
Casson AG, Manolopoulos B, Troster M, et al: Clinical implications of p53 gene mutation in theprogression of Barrett's epithelium to invasive oesophageal cancer. Am J Surg 167:52–57, 1994
Sauter ER, Keller SM, Erner SM: p53 correlates with improved survival in patients with esophageal adenocarcinoma. J Surg Oncol 58:269–273, 1995
Hamelin R, Flejou JF, Muzeau F, et al: TP53 gene mutations and p53 protein immunoreactivity in malignant and premalignant Barrett's oesophagus. Gastroenterology 107:1012–1018, 1994
Hameeteman W, Tytgat GNJ, Houthoff HJ, et al: Barrett's oesophagus: Development of dysplasia and adenocarcinoma. Gastroenterology 96:1249–56, 1989
Jankowski J: Flow cytometric assessment of regulatory peptides in Barrett' s mucosa. Gastroenterology 102:1121, 1992 ( letter)
Bennett WP: p53 alterations in progenitor lesions of the bronchus, oesophagus, oral cavity and colon. Cancer Det Prev 19(6):503–511, 1995
Ireland AP, Clark GWB, De Meester TR: Barrett' s oesophagus: The significance of p53 in clinical practice. Ann Surg 225( 1):17–30, 1997
Krishnadath KK, Tilanus HW, Alers JC, et al: Detection of genetic changes in Barrett' s adenocarcinoma and Barrett's oesophagus by DNA in situ hybridization and Immunohistochemistry. Cytometry 15:176–184, 1994
Iannettoni MD, Lee SS, Bonnell, Sell TL, Whyte RI, Orringer MD, Beer DG: Detection od Barrett' s adenocarcinoma of the gastric cardia with sucrase isomaltase and p53. Ann Thorac Surg 62:1460–1465, 1996
Liang Y, Esteve A, Martel-Planche G, Takahashi S, et al: p53 mutations in oesophageal tumors from high-incidenceareas of China. Int J Cancer: 61:611–614, 1995
Hardwick RH, Shepherd NA, Moorghen M, Newcomb PV, Alderson D: Adenocarcinoma arising in Barrett' s oesophagus: evidencefor the participation of p53 dysfunction in the dysplasia/ carcinoma sequence. Gut 35(6):764–768, 1994
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Kubba, A.K., Poole, N.A. & Watson, A. Role of p53 Assessment in Management of Barrett's Esophagus. Dig Dis Sci 44, 659–667 (1999). https://doi.org/10.1023/A:1026608319881
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DOI: https://doi.org/10.1023/A:1026608319881