Her-2/neu in Barrett’s esophagus: a comparative study between histology, immunohistochemistry, and fluorescence in situ hybridization

Her-2/neu is a protooncogene frequently overexpressed in breast cancer, recently found to be also overexpressed in carcinoma arising on Barrett esophagus (BE). Immunohistochemistry and fluorescence in situ hybridization (FISH) are conventionally used for Her-2 testing in carcinomas, but a single assay is not yet accepted as a "gold standard" in BE. To evaluate the correlation between histopathology variables and gene expression/amplification in the sequence BE-low grade dysplasia-high grade dysplasia-adenocarcinoma, fifty esophageal specimens from patients with a diagnosis of BE (21 BE, 4 low-grade dysplasia, 12 high-grade dysplasia, and 13 adenocarcinomas) were evaluated. Histopathologic evaluation was carried out using hematoxylin and eosin staining. Paraffin-embedded tissues were investigated for Her-2 by immunohistochemistry (HercepTest) and FISH. HercepTest was scored 0, 1+, 2+, and 3+ depending on the percentage (cut off 10%) of membrane staining, whereas gene assessment evaluated by FISH was based on the ratio between Her-2/neu and the 17 chromosome copy number. There was a positive correlation between gene amplification and protein overexpression. No case with HercepTest scoring 0 or 1+ displayed gene amplification, but this was present in 20% of cases scoring 2+ and in all cases scoring 3+. Her-2/neu amplification or overexpression was never observed in BE. Gene amplification and overexpression was observed in more than 50% of dysplasias and adenocarcinomas. Her-2/neu amplification/overexpression might be considered as a marker of progression from BE to dysplasia. FISH may represent a useful diagnostic tool to integrate the result of HercepTest for selecting patients for more targeted therapeutic approaches.