Chromosome 4 hyperploidy occurs early in premalignant Barrett’s oesophagus

Genetic aberrations are widespread in Barrett’s oesophagus, with aneuploidy developing well before dysplasia can be identified.

Endoscopic cytology brushings from patients with oesophageal dysplasia, Barrett’s metaplasia, and adenocarcinoma were cytospun to generate a single layer of interphase cells. The slides were prepared for FISH and examined with chromosome enumeration probes for the centromeres of chromosomes 4,8,20 and locus specific identifier probes for p53, 13q14 and 9p21/CEP9.

Chromosome 4 hyperploidy proved the commonest alteration, present in 89% of Barrett’s patients, persisting in low grade dysplasia (LGD) and high grade dysplasia (HGD). The proportion of cells displaying this hyperploidy increased with neoplastic progression.

Chromosome 8 hyperploidy was also prominent being present in 71% of metaplastic Barrett’s patients, 75% of those with LGD and all those with HGD and adenocarcinoma.

Both losses and gains in chromosome 20 were detected. Only four of 20 men with metaplasia had lost chromosome Y but this increased to 38% in LGD, 71% in HGD, and 100% in adenocarcinoma.

The study has identified genetic instability in Barrett’s metaplastic tissues, predominantly of chromosomes 4 and 8. This amplification may point to key genes on the chromosomes being mechanistically involved in initiation and progression of the lesion. Additionally, brush cytology coupled to FISH analysis is a suitable technique to identify early genetic abnormalities.