Clinical implications of p53 gene mutation in the progression of Barrett's epithelium to invasive esophageal cancer

Casson, Alan G.; Manolopoulos, Bill; Troster, Michael; Kerkvliet, Nancy I.; O’Malley, Frances P.; Inculet, Richard; Finley, Richard J.; Roth, Jack A.

doi:10.1016/0002-9610(94)90053-1

Cited by 66 publications

(30 citation statements)

References 20 publications

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“…This is probably due to the purity of our cell population obtained by selection of specific cells by LCM, and direct sequencing of PCR products in both directions, rather than using indirect techniques. 7,12,15,16,18,[23][24][25][26][27][28][29] Therefore, the role of p53 mutation as a prognostic factor in progression of metaplastic BE toward esophageal adenocarcinoma is not certain. Since the molecular basis of p53 function and mutations is not fully understood, a better evaluation of the biological properties of different p53 mutations is needed in order to interpret the results.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of p53 mutations in premalignant esophageal lesions and esophageal adenocarcinoma using laser capture microdissection

et al. 2004

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p53 mutations have been implicated in the development of esophageal malignancies. The purpose of this study was to assess more accurately the incidence and types of p53 mutations in Barrett's esophagus (BE) with and without dysplasia and in esophageal adenocarcinoma, using pure preparations of epithelial cells obtained by laser capture microdissection (LCM). Assays were performed on paraffin-embedded tissue samples of normal antrum and premalignant and malignant esophageal samples from 57 patients, including 16 controls, 10 with BE metaplasia alone, 20 with BE-associated dysplasia, and 11 with BE-associated adenocarcinoma. All tissues were processed for LCM. DNA was extracted from isolated cells, and polymerase chain reaction (PCR) was performed using oligonucleutide primers for exons 5-8 of p53. PCR products were processed for DNA sequencing. p53 sequence abnormalities were identified in 2/16 cases of normal antrum and regenerative/ chemical gastritis, 1/10 cases of BE, 1/20 cases of BE with dysplasia, and 2/11 cases of adenocarcinomas. The abnormalities occurred in exons 7 and 8 in the form of point mutations. Our results, using LCM, show that p53 gene mutations are relatively rare in esophageal preneoplastic and neoplastic conditions. Only point mutations were detected, but no deletions/insertions were identified.

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Section: Discussionmentioning

confidence: 99%

Evaluation of p53 mutations in premalignant esophageal lesions and esophageal adenocarcinoma using laser capture microdissection

et al. 2004

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“…For this reason, p53 overexpression does not always correlate with p53 gene mutations (36,38,39). In the above study from Coggi et al, 35 tumors without p53 mutation were identified.…”

Section: Relationship Between P53 Mutations and Immunohistochemical Ementioning

confidence: 99%

Clinical Use of p53 in Barrett's Esophagus

Keswani¹,

Noffsinger

Waxman³

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Barrett's esophagus is an established precursor to esophageal adenocarcinoma. Whereas most patients with Barrett's esophagus do not progress to adenocarcinoma, patients with progression have a poor prognosis. Current management strategies use frequent endoscopic surveillance and multiple nontargeted biopsies. This approach, however, may miss dysplastic areas. Furthermore, given the relatively high prevalence of Barrett's esophagus but low incidence of progression, this invasive and expensive approach has not been shown to be cost-effective. Thus, there is intense interest in using biomarkers to identify patients at increased risk of progressing to adenocarcinoma. This has included examination of mutations in the tumor suppressor gene, p53. In this report, we discuss the biology of p53 and the incidence of p53 mutations in Barrett's esophagus and review relevant studies regarding the ability of p53 to predict neoplastic progression. Additionally, we report our results of the expression of p53 by immunohistochemistry in a group of 18 patients that have undergone endoscopic esophageal mucosal resection for dysplasia. Although the presence of a p53 mutation increases the risk of neoplastic progression, the absence of this mutation does not abrogate the risk. Continuing efforts, therefore, are needed to define and prospectively validate a panel of biomarkers to risk-stratify patients with Barrett's esophagus. Determination of p53 mutational status may ultimately be a component of such a panel. (Cancer Epidemiol Biomarkers Prev 2006;15(7):1243 -9)

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“…Genetic alterations involving the p53 TSG are amongst the most commonly found abnormality, present in many di erent tumours (Harris and Hollstein, 1993;Greenwald et al, 1992;Wang and Wang, 1996). In Barrett's oesophagus loss of heterozygosity (LOH), mutation and overexpression of the p53 TSG occurs frequently and in most cases precedes the development of invasive cancer (Gleeson et al, 1995;Krishnadath et al, 1995;Flejou et al, 1994;Casson et al, 1994;Blount et al, 1994;Galipeau et al, 1996;Audrezet et al, 1996;Campomenosi et al, 1996;Neshat et al, 1994;Gonzalez et al, 1997). Other genetic abnormalities found in BOA include LOH, homozygous deletion and mutation within the MTS1/p16 TSG at 9p21 (Gonzalez et al, 1997;Barrett et al, 1996a), LOH on 5q, 13q and 18q Blount et al, 1993), aneuploidy (Barrett et al, 1996b;Blount et al, 1994;Galipeau et al, 1996), and the ampli®cation and overexpression of certain oncogenes, notably c-erbB-2 and EGF-R. (Filipe and Jankowski, 1993;AlKasspooles et al, 1993;Nakamura et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Multiple target sites of allelic imbalance on chromosome 17 in Barrett's oesophageal cancer

et al. 1999

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Twelve Barrett's adenocarcinomas have been analysed for the occurrence of allelic imbalance (LOH) on chromosome 17 using 41 microsatellite markers. This study provides evidence for 13 minimal regions of LOH, six on 17p and seven on 17q. Four of these centre in the vicinity of the known tumour suppressor genes (TSGs) TP 53 (17p13.1), NF1 (17q11.2), BRCA1 (17q21.1), and a putative TSG (17p13.3). The tumours all displayed relatively small regions of LOH (1 ± 10 cM), and in several tumours extensive regions of LOH were detected. One tumour displayed only two very small regions of LOH; 17p11.2 and 17p13.1. The frequency of allelic imbalance has been calculated based on the LOH encompassing only one minimal region, and based on all the LOH observations. By both evaluations the highest LOH frequencies were found for regions II (p53), III (17p13.1 centromeric to p53), IV (17p12), V (17p11.2) and VII (NF1, 17q11.2). Our data supports the existence of multiple TSGs on chromosome 17 and challenges the view that p53 is the sole target of LOH on 17p in Barrett's adenocarcinoma.

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Clinical implications of p53 gene mutation in the progression of Barrett's epithelium to invasive esophageal cancer

Cited by 66 publications

References 20 publications

Evaluation of p53 mutations in premalignant esophageal lesions and esophageal adenocarcinoma using laser capture microdissection

Evaluation of p53 mutations in premalignant esophageal lesions and esophageal adenocarcinoma using laser capture microdissection

Clinical Use of p53 in Barrett's Esophagus

Multiple target sites of allelic imbalance on chromosome 17 in Barrett's oesophageal cancer

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