B. Trautmann et al., K-RAS POINT MUTATIONS ARE RARE EVENTS IN PREMALIGNANT FORMS OF BARRETTS-ESOPHAGUS, European journal of gastroenterology & hepatology, 8(8), 1996, pp. 799-804
Objective: In Barrett's adenocarcinomas, in contrast to squamous oesop
hageal carcinomas, K-ras point mutations are thought to be a frequent
event. The frequency of K-ras point mutations in premalignant forms of
Barrett's oesophagus (metaplasia, dysplasia) leading to adenocarcinom
a with increased risk is currently not known. To establish the frequen
cy of K-ras mutations in premalignant forms of Barrett's oesophagus, w
e investigated oesophageal biopsy specimens with Barrett's metaplastic
and dysplastic epithelium for point mutations in the K-ras gene/codon
s 12, 13. Design: A total of 412 biopsies from patients with Barrett's
oesophagus were histologically classified into biopsies with metaplas
ia (n=252), dysplasia (n=105) and adenocarcinoma (n=11), as well as bi
opsies distant from disease (normal, n=37 and hyperplastic squamous ep
ithelium, n=7). Methods: DNA from biopsy specimens was amplified by po
lymerase chain reaction (PCR) with a modified primer for generating a
restriction site in the case of wild type in codon 12. Wild-type or po
int mutations in the K-ras gene/codons 12, 13 were detected by restric
tion fragment length analysis of the PCR products. Results: Point muta
tions in K-ras/codon 12 were found in 9 biopsies (n=1 in metaplasia, n
=4 in dysplasias, n=4 in adenocarcinomas). All the other biopsies show
ed the wild type of K-ras/codon 12. No K-ras/codon 13 mutation (GGC(gl
y)-->GAC(asp)) was observed. Conclusion: Mutations in K-ras/codon 12 w
ere rarely found in premalignant forms of Barrett's oesophagus. Wherea
s the screening for K-ras point mutations in metaplastic sites of Barr
ett's epithelium seems not to be of practical value, the screening for
mutations in dysplastic lesions might be helpful to estimate the indi
vidual risk for progression of Barrett's epithelium to adenocarcinoma.
A further evaluation in larger numbers of patients is needed.