title: Evaluation of Her-2/neu status in carcinomas with amplified chromosome 17 centromere locus.
abstract: Accurate assessment of Her-2/neu (erb-b2) status in breast carcinoma is essential for therapy planning. Clinical assays are targeted at protein overexpression (immunohistochemical analysis) or gene amplification (fluorescence in situ hybridization [FISH]). Cases with aberrant FISH signal patterns are problematic and may lead to underreporting of Her-2/neu amplification. We performed FISH with additional chromosome 17 probes, SMS (Smith-Magenis syndrome critical region) and RARA (retinoic acid receptor), on 7 cases with unusual Her-2/CEP17 (chromosome 17 centromere control probe) results to assess whether different measurements of chromosome 17 copy number might clarify the Her-2/neu amplicon status. Although the Her-2/CEP17 ratio scores were within normal range (<2.0), the Her-2/SMS or Her-2/RARA ratio revealed amplification of Her-2/neu in 5 of 7 cases. Immunohistochemical analysis demonstrated Her-2/neu protein overexpression in the same 5 cases only. We describe novel application of SMS/RARA FISH probes for assessing cases with complex Her-2/CEP17 FISH patterns. Such additional data, correlated with immunohistochemical analysis, may help guide therapy in patients with breast carcinoma.
authors.affiliation: Department of Pathology, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Troxell
authors.forename: Charles D
authors.initials: CD
authors.lastname: Bangs
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Lawce
authors.forename: Ilana B
authors.initials: IB
authors.lastname: Galperin
authors.forename: Daniel
authors.initials: D
authors.lastname: Baiyee
authors.forename: Robert B
authors.initials: RB
authors.lastname: West
authors.forename: Susan B
authors.initials: SB
authors.lastname: Olson
authors.forename: Athena M
authors.initials: AM
authors.lastname: Cherry
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002503:Centromere / Q000235:genetics; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; C000607071:RARA protein, human