¹Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

Correspondence: Dr O Kocher, MD, PhD, Department of Pathology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215, USA. E-mail: okocher@bidmc.harvard.edu

Received 21 April 2004; Revised 2 June 2004; Accepted 2 June 2004; Published online 16 July 2004.

Abstract

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.