K-ras codon 12 mutations in Barrett's oesophagus and adenocarcinomas of the oesophagus and oesophagogastric junction

Background: Activation of the ras oncogene is commonly found in gastrointes tinal tract cancers, but the role of ras in the development and progression of Barrett's oesophagus and associated cancers is uncertain. Methods: The frequency of K-ras codon 12 point mutations was assessed in 52 paraffin-embedded tissues from 44 patients with oesophageal pathology. The specimens were classified pathologically as follows: adenocarcinoma of the oesophagus or oesophagogastric junction (n = 23), Barrett's high-grade dys plasia (n = 5), low-grade dysplasia (n = 14), intestinal metaplasia (n = 4) , normal oesophagus (n = 5) or normal stomach (n = 1). DNA was extracted fr om three consecutive sections of each paraffin block and mutations at bases 1 and 2 of K-ras codon 12 were identified using a novel restriction endonu clease-mediated selective polymerase chain reaction method. Results: Mutations were found in 7 of 23 (30.4%) adenocarcinomas and in 2 o f 5 (40%) high-grade dysplasia specimens. No mutations were found in specim ens of low-grade dysplasia, intestinal metaplasia without dysplasia, or nor mal oesophagus and stomach. There were no significant associations between the presence of mutations and clinicopathologic features in the patients wi th cancer. One patient who progressed from low-grade to high-grade dysplasi a was found to have developed mutant K-ras in the course of this transforma tion. Conclusion: These results suggest that K-ras codon 12 mutations may occur f requently in patients with Barrett's oesophagus with high-grade dysplasia o r adenocarcinoma of the oesophagus or oesophagogastric junction. K-ras muta tion may be a late event in the Barrett's metaplasia-dysplasia-adenocarcino ma sequence. (C) 2000 Blackwell Science Asia Pty Ltd.