TOPOIIalpha and HER-2/neu overexpression/amplification in Barrett's oesophagus, dysplasia and adenocarcinoma.

AIMS: Topoisomerase IIalpha (TOPOIIalpha) and HER-2/neu are chromosome 17q genes coamplified in various cancers; no data exist for Barrett's oesophagus (BO) and BO adenocarcinoma (ADC). The aim was to investigate gene amplification and protein overexpression of TopoIIalpha and Her-2/neu in non-dysplastic BO, dysplastic BO, Barrett ADC, and chromosome 17 aneusomy.

METHODS AND

RESULTS

Forty-four patients [18 BO, 13 BO with dysplasia (five low-grade dysplasia, eight high-grade dysplasia) and 13 ADC in BO] were evaluated by immunohistochemistry and fluorescence in situ hybridization (FISH). Genes (HER-2/neu and TOPOIIalpha) and chromosome 17 were evaluated by FISH. Patients with BO, dysplasia and ADC were compared. A significant association was found between TOPOIIalpha protein overexpression and TopoIIalpha gene amplification, chromosome 17 aneusomy, HER-2/neu gene amplification and HER-2 protein overexpression as well as between HER-2 protein and HER-2/neu gene, TopoIIalpha gene and aneusomy for chromosome17, and between the genes TOPOIIalpha and HER-2/neu. Gene amplification (HER-2/neu, TOPOIIalpha), protein overexpression (HER-2/TOPOIIalpha), and chromosome 17 aneusomy were associated with dysplasia or ADC. Most BO patients showed no amplification/overexpression/aneusomy for the above genes, proteins and chromosome, with no differences between dysplasia and ADC.

CONCLUSIONS

HER-2/neu and TOPOIIalpha amplification/overexpression might discriminate between BO and dysplasia/ADC. Chromosome 17 aneusomy is associated with dysplasia or ADC in BO.