Clinical Significance of p53 Mutations in Adenocarcinoma of the Esophagus and Cardia

Abstract

ObjectiveTo compare the frequency and spectrum of p53 gene mutations in adenocarcinomas of the esophagus and cardia and to compare clinical and pathologic features in patients with p53 mutant and nonmutant cancers. Summary Background DataThe p53 gene is commonly mutated in human cancers, and a p53 mutation is reported to be present in more than 50% of esophageal adenocarcinomas. Although many studies have investigated the frequency of p53 protein overexpression in adenocarcinomas of the esophagus or esophagogastric junction, few studies have assessed the frequency and clinical significance of p53 mutations in these tumors. In particular, the prognostic importance of p53 mutation is uncertain. Adenocarcinomas of the esophagus and cardia share many epidemiologic and pathologic features, but it is controversial whether they represent the same tumor. A comparison of the frequency and spectrum of mutations in adenocarcinomas of the esophagus and cardia would test whether these tumors are also similar at the molecular level. MethodsDNA was isolated from microdissected paraffin-embedded tumor tissues of patients who underwent esophagogastrectomy for adenocarcinoma of the esophagus (n ϭ 19), cardia (esophagogastric junction, n ϭ 12), or subcardia (n ϭ 6). Exons 5 to 8 of the p53 gene were analyzed for the presence of mutations using the polymerase chain reaction with singlestrand conformation polymorphism and DNA sequencing of bands showing abnormal mobility. The presence of mutation was confirmed by selective hybridization of a mutant-specific oligonucleotide to DNA isolated from the tumor. Resultsp53 mutations were identified in 18 of 37 (48.6%) tumors. Patients with p53 mutant tumors were significantly younger and had a significantly poorer prognosis. There was a similar prevalence of p53 mutations in adenocarcinomas of the esophagus (53%) and cardia (58%). In contrast, mutations were relatively uncommon in subcardia adenocarcinomas (one mutant tumor [17%]). The types of mutations found in the esophageal and the cardia cancers were also similar.

Mucin phenotypic expression and background mucosa of esophagogastric junctional adenocarcinoma

“…Of our EGJ-type tumors, 52% reacted with human gastric mucin, but many of them also reacted with intestinal mucin, and many of the bEGJtype tumors were of the pure intestinal phenotype. High levels of p53 protein expression have been reported in gastric cardia tumors (56%-65%) and also in esophageal adenocarcinoma (59%), in comparison to levels in adenocarcinoma of the antrum (27%) [7,8]. In the present series, 78% of the EGJ-type and 55% of bEGJtype tumors expressed p53 protein.…”

“…We investigated tumors less than 4 cm in maximum diameter, because the architecture of the EGJ was still preserved in the presence of such small tumors, and the background mucosae of the carcinoma, in terms of the squamocolumnar junction (SCJ), cardiac glands, oxyntic glands, intestinal metaplasia, and Barrett's epithelium, were easily studied. We also investigated p53 protein overexpression, because significantly high levels of p53 mutations and p53 protein overexpression in cardia and esophageal adenocarcinomas have been reported in the West [7,8]. In this study, we investigated the characteristics of junctional carcinoma and background mucosa in Japanese patients to find the similarities with and differences from Western patients.…”

Adenocarcinoma of the esophagogastric junction: relationship between clinicopathological data and p53, cyclin D1 and Bcl-2 immunoexpressions

“…The results of the p53 immunoexpression in this investigation did not associate with the postoperative survival (P = 0,303) and, also did not present any association with the clinicopathological parameters by univariate analysis. These findings are in accordance with other published data (5,6,7,17,18,21,23,25,31,36,39) . IRELAND et al (17) verified p53 mutations in 48.6% of the studied adenocarcinomas, being 53% of esophagus and 58% of the cardia.…”

Characterisation of p53 status at the gene, chromosomal and protein levels in oesophageal adenocarcinoma

“…The result is an accumulation of errors in the genome, which is passed onto daughter cells thus aiding neoplastic progression. This may explain why Barrett's patients with p53 mutations have more advanced tumours, significantly worse prognosis and are on average 15 years younger than those without such alterations (Ireland et al, 2000). As these mutated p53 molecules have an altered conformation and can no longer form a complex with Mdm2, they are not degraded.…”