title: The influence of polysomy 17 on HER2 gene and protein expression in adenocarcinoma of the breast: a fluorescent in situ hybridization, immunohistochemical, and isotopic mRNA in situ hybridization study.
abstract: Breast carcinomas with amplification of HER2 on chromosome 17 are associated with HER2 protein overexpression, adversely affecting prognosis and predicting response to Herceptin therapy. Chromosome 17 polysomy is encountered in assessing HER2 gene status, and its impact on HER2 gene and protein expression remains unclear. This impact was investigated in breast carcinomas identified by fluorescence in situ hybridization (FISH) to have a gain of chromosome 17 (CEP17+; n = 56), using a dual probe assay, which detects HER2 gene copy number and enumerates chromosome 17 (HER2/CEP17; Vysis). Cases were immunostained for HER2 protein (CB-11, Ventana), and scored blinded to FISH. A subgroup was evaluated by isotopic in situ hybridization for HER2 mRNA expression. Controls included ten HER2 amplified and ten nonamplified tumors, eusomic for chromosome 17. Immunohistochemistry (IHC) for HER2 protein was negative (0 or 1+) in 69% (39 of 56), 2+ in 27% (15 of 56), and 3+ in 3% (2 of 56) of CEP17+ cases. The mean CEP17 copy number among the three groups was similar (3.1, 3.0, and 3.1 for IHC 0/1+, 2+, and 3+, respectively). Isotopic in situ hybridization for HER2 mRNA performed on 26 CEP17+ cases (16 IHC 0-1+, 10 IHC 2+ or 3+) showed no increased HER2 mRNA expression (normalized to beta-actin mRNA). The mRNA expression and the IHC staining of the HER2-amplified and nonamplified controls was concordant with their FISH status. These results suggest that chromosome 17 polysomy in the absence of HER2 amplification does not have a significant biologic influence on HER2 gene expression in breast carcinoma.
authors.affiliation: Department of Anatomical and Clinical Pathology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Erinn
authors.initials: E
authors.lastname: Downs-Kelly
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Yoder
authors.forename: Mark
authors.initials: M
authors.lastname: Stoler
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Tubbs
authors.forename: Marek
authors.initials: M
authors.lastname: Skacel
authors.forename: Thomas
authors.initials: T
authors.lastname: Grogan
authors.forename: Patrick
authors.initials: P
authors.lastname: Roche
authors.forename: David G
authors.initials: DG
authors.lastname: Hicks
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D018734:Genes, erbB-2 / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D012333:RNA, Messenger