title: Suggestions for HER-2/neu testing in breast carcinoma, based on a comparison of immunohistochemistry and fluorescence in situ hybridisation.
abstract: The arrival of Herceptin (Trastuzumab), an antibody against the HER-2 oncogene found in a proportion of breast carcinomas and other carcinomas, has emphasised the need for a standardised technique for demonstrating overexpression of HER-2. We compared the Dako A485 antibody and Dako HercepTest kit (HT) on a series of 122 breast carcinomas. Fluorescence in situ hybridisation (FISH) (Vysis) was performed on all cases with positive or equivocal immunohistochemical results. The Dako A485 showed HER-2 overexpression in 53% of carcinomas, while the HT showed 21% positive (HT 2+ 8%, HT 3+ 13%) and 79% negative (HT 0 67%, HT 1+ 12%). FISH for HER-2 gene amplification on all the HT 1+ and HT 2+ cases was negative, whereas FISH analysis of all HT 3+ cases was positive, with the exception of one case which could not be analysed for technical reasons. When histological subtype was analysed, only grade 3 infiltrating duct carcinomas were FISH-positive, suggesting that histological grading and subtyping may be able to triage carcinomas suitable for HER-2 testing. We suggest that the HT or a similar standardised immunohistochemical study for HER-2 can be used to screen breast carcinomas. We then recommend FISH where the carcinoma is HT 2+. FISH may also be appropriate in high grade, HT 1+ carcinomas where there are doubts regarding optimal tissue fixation or block storage conditions.
authors.affiliation: Department of Anatomical Pathology, St Vincent's Hospital, Sydney, Australia.
authors.forename: A S
authors.initials: AS
authors.lastname: Field
authors.forename: N L
authors.initials: NL
authors.lastname: Chamberlain
authors.forename: D
authors.initials: D
authors.lastname: Tran
authors.forename: A L
authors.initials: AL
authors.lastname: Morey
mesh_terms: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology; D002503:Centromere; D002886:Chromosomes, Human, Pair 17; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000235:genetics*; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004273:DNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab