p53 protein in esophageal mucosa of individuals at high risk of squamous cell carcinoma of the esophagus

Abstract

Squamous cell carcinoma of the esophagus (SCCE) is diagnosed late and carries a poor prognosis. Biomarkers such as p53 protein expression may be present in the esophageal mucosa long before esophageal symptoms or lesions appear and may point toward early diagnosis. Asymptomatic subjects at high risk for SCEE (consumption of more than 80 g of ethanol and 10 cigarettes/day for at least 10 years) underwent upper gastrointestinal endoscopy with biopsies of the esophageal mucosa, and expression of p53 protein was compared with conventional histologic findings. In 182 subjects studied, p53 protein was expressed in a stepwise fashion according to the severity of the histologic findings: normal mucosa (12/103 or 11.7%), mild chronic esophagitis (6/43 or 14%), moderate chronic esophagitis (4/18 or 22.2%), severe chronic esophagitis (1/3 or 33.3%), low-grade dysplasia (4/11 or 36.4%), high-grade dysplasia (2/2 or 100%), and squamous cell carcinoma (2/2 or 100%) (P=0.00025). The odds ratio and confidence intervals were calculated by logistic regression, with multivariate adjustment for potentially confounding variables. The risk for p53 expression was twofold for moderate and severe chronic esophagitis and 10-fold for dysplasia and cancer (P=0.001). p53 protein was expressed not only in cancerous lesions, high-grade and low-grade dysplasia, as expected, but also in mucosa considered normal or with chronic esophagitis using conventional histology. Smokers and alcohol drinkers with normal mucosa or chronic esophagitis that express p53 protein may represent an unrecognized subgroup of individuals that may benefit from surveillance. Follow-up studies of these asymptomatic subjects and molecular analysis of the p53 gene are needed to clarify this point.

Detecting p53 Immunoexpression inEsophageal Mucosa with Exfoliative Cytologyin Individuals at Risk for Squamous CellCarcinoma of the Esophagus

“…In the present study we found few cases of dysplasia/carcinoma; however, a quarter of the subjects studied expressed p53 protein in their esophageal mucosa associated with the severity of the histologic findings, as previously reported by Fagundes et al 21 and Ohbu et al 30 Contrary to our expectations there was no identification of p53 protein expression in cytologic smears. The negative expression of p53 protein in cytologic samples from individuals with positive expression in biopsies produced 2 questions: (1) Were cytologic smears adequate material in which to look for p53 protein expression?…”

“…On the basis of the results of Fagundes et al, 21,22 we calculated that it would require 134 patients to detect a 17% positivity of p53 expression in esophageal mucosa of high-risk individuals, considering a statistical power of 90% and a confidence interval of 95%. Data analysis was conducted with SPSS (Chicago, Illinois, U.S.A.).…”

“…Previous studies suggested that its expression in biopsies of individuals at risk for SCCE could be useful to identify subjects with greater risk for SCCE. 21,22 Therefore, we chose to study the expression of p53 protein as a potential marker in cells sampled, through an exfoliative cytology technique, from individuals with risk factors for SCCE.…”

“…Therefore, p53 may be used as an early molecular marker of SCCE. [15][16][17][18][19][20] Studies published by Fagundes et al 21 on the Rio Grande do Sul state in Brazil showed that patients at high risk for SCCE express p53 protein in a stepwise fashion according to the severity of the histologic findings. Immunohistochemical p53 protein expression was not found in healthy individuals.…”

Statistical Evaluation and Correlative Study of Neoplastic and Non-Neoplastic Lesions of Oesophagus

“…11,12 Implicated genes including those involved in cell signalling, cell cycle control, cell adhesion and apoptosis are well characterised and their expression levels are known to be altered in oesophageal carcinogenesis.…”