Expression of the RB protein, allelic imbalance of the RB gene and amplification of the CDK4 gene in metaplasias, dysplasias and carcinomas in Barrett's oesophagus.

In the present study, the role of allelic loss at the retinoblastoma gene (RB), expression of the retinoblastoma protein (pRb) and amplification at the CDK4 gene in the metaplasia--dysplasia--carcinoma sequence in Barrett's oesophagus (BO) was investigated. Samples of metaplastic specialised epithelium (SE; n = 28), low-grade dysplasia (LGD; n = 21), high-grade dysplasia (HGD; n = 19) and invasive adenocarcinoma (CA; n = 35) derived from 36 oesophagectomy specimens were included. Of the cases that were informative for the RB gene (n = 27), loss of heterozygosity (LOH) was found in none of the 22 SE, in none of the 14 LGD, in 1 of the 12 HGD (8.3%) and in 5 of the 27 CA (18.5%). Immunohistochemically, an enhanced expression of pRb protein in LGD, HGD and CA as compared with SE was found in most cases. In 4 carcinoma samples, however, a marked reduction (3 cases) or complete absence (1 case) of pRb protein expression was found. Two out of these 4 CA samples showed LOH in the RB gene whilst one case was heterozygous and one case was homozygous. In contrast to the positive controls used, CDK4 amplification was not detectable by means of differential PCR in any of the samples under investigation. The present study indicated that allelic loss of the RB gene occurs late in the metaplasia--dysplasia--carcinoma sequence in BO. Immunohistochemically determined loss of pRb protein expression may indicate LOH of the RB gene. CDK4 gene amplification does not seem to play a role in the development of oesophageal adenocarcinoma.