title: HER-2 overexpression/amplification in Barrett's oesophagus predicts early transition from dysplasia to adenocarcinoma: a clinico-pathologic study.
abstract: Barrett's oesophagus (BO) is the primary precursor lesion for oesophageal adenocarcinoma (ADC). The natural history of metaplasia-dysplasia-carcinoma sequence remains largely unknown. HER2/neu oncogene results overexpressed/amplified in preneoplastic lesions and in ADC of the oesophagus and it has been associated with poor prognosis. Our aim was to evaluate the role of HER2 overexpression/amplification in predicting the conversion from precursor lesions to ADC. We retrospectively evaluated by univariate analysis of single variables clinical records and histological specimens of 21 patients with a confirmed diagnosis of BO and/or oesophageal dysplasia. Clinical variables included age, gender, alcohol and smoking intake, presence of symptoms (pyrosis, disphagia) and endoscopic features (length). HER2 status was studied by immunohistochemistry and fluorescence in situ hybridization (FISH) on paraffin-embedded tissue. The end-points were the occurrence of progression and the time-to-progression (TTP) from the initial histologic lesion to the worst pathological pattern. Median age at diagnosis was 63 years (range 37-84). BO median length was 4.5 cm. Progression occurred in 11 of 21 patients and median TTP was 24 months. HER2 was overexpressed/amplified in 8 of 21 (38%) patients. HER2 overexpression/ amplification and the presence of dysplasia were statistically associated with progression (P= 0.038). This study provides evidence for a possible role of HER2 in the transition from dysplasia to ADC of the oesophagus. This fact could help in identifying patients at high risk of malignant transformation.
authors.affiliation: 2nd Department of Pathology, Spedali Civili, Brescia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Rossi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Grisanti
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Villanacci
authors.forename: Domenico
authors.initials: D
authors.lastname: Della Casa
authors.forename: Paolo
authors.initials: P
authors.lastname: Cengia
authors.forename: Guido
authors.initials: G
authors.lastname: Missale
authors.forename: Luigi
authors.initials: L
authors.lastname: Minelli
authors.forename: Michela
authors.initials: M
authors.lastname: Buglione
authors.forename: Renzo
authors.initials: R
authors.lastname: Cestari
authors.forename: Gabrio
authors.initials: G
authors.lastname: Bassotti
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; 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; D016896:Treatment Outcome
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human