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


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.
Rossi
Elisa
E
2nd Department of Pathology, University of Brescia-Spedali Civili, Brescia, Italy.
Villanacci
Vincenzo
V
Bassotti
Gabrio
G
Donato
Francesco
F
Festa
Andrea
A
Cengia
Gianpaolo
G
Grisanti
Salvatore
S
Cestari
Renzo
R
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D001471:Barrett Esophagus / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D003937:Diagnosis, Differential; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D018734:Genes, erbB-2; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies
D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human