Clinical Use of p53 in Barrett's Esophagus

Abstract

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)

Prevalence of Barrett’s Esophagus in Patients with or without GERD Symptoms: Role of Race, Age, and Gender

“…Our findings are consistent with a previous study that suggested that fewer than 5% of patients with adenocarcinoma of the esophagus have known BE prior to the diagnosis of adenocarcinoma [19]. Recent studies regarding testing with biomarkers may hold promise for the future [20][21][22][23].…”

Corn-derived carbohydrate inositol hexaphosphate inhibits Barrett's adenocarcinoma growth by pro-apoptotic mechanisms

“…These cell lines are useful in that one is wild-type p53 (SEG1) while the other is mutated (BIC-1). p53 mutation has been associated with Barrett's aggressiveness, and may be an early stage in the transformation of benign to malignant epithelium (26). This data in conjunction with the other studies cited above indicates that IP6 may have the potential to become an effective adjuvant treatment for Barrett's adenocarcinoma.…”

Expression of α-methylacyl coenzyme A racemase in the dysplasia carcinoma sequence associated with Barrett’s esophagus

“…TP53 was found to have a low sensitivity, but p53 mutational status may ultimately be a component of such a molecular marker panel. 4,20 C-erbB2/Her-2/neu could not be demonstrated as a molecular marker by Langer et al 18 but fluorescence in situ hybridization (FISH) analysis demonstrated amplification/overexpression of Her-2/neu as a marker of progression from Barrett's epithelium to dysplasia. 22 The authors suggested that FISH represents a useful diagnostic tool for selecting patients for more targeted therapeutic approaches.…”

“…3 Although most patients with Barrett's esophagus do not progress to adenocarcinoma, those with progression have a poor prognosis. 4 Endoscopic resection has been recommended as a local curative approach for (unicentric) mucosal Barrett's adenocarcinoma (m1 or m2, and m3 without lymph vessel infiltration). 5 Surgery is still the therapy of choice in early Barrett's adenocarcinoma infiltrating submucosal layers or poorly differentiated tumors because of a higher risk of lymph-node metastasis.…”