title: Her-2/neu and topoisomerase IIα in advanced breast cancer: a comprehensive FISH analysis of 245 cases.
abstract: Her-2/neu gene amplification is an established prognostic factor in breast cancer, and Her-2/neu protein is the target of the therapeutic monoclonal antibody Herceptin. More recently, topoisomerase IIα became a new focus of breast cancer research because of its role as a target for anthracycline therapy. Therefore, we compared Her-2/neu and topoisomerase IIα amplification/deletion in a large series of advanced breast cancer using fluorescence in situ hybridization. Paraffin-embedded archival tissue from 245 patients was retrieved and assessed for Her-2/neu and topoisomerase IIα amplification/deletion by fluorescence in situ hybridization according to standard protocols. Relation to clinical data and survival was sought. A total of 245 cases were analyzed. Amplification for Her-2/neu was seen in 57 cases (23.3%), and for topoisomerase IIα in 12 cases (4.9%). Coamplification was found in 9 samples (3.7%), 3 cases (1.2%) showed amplification of topoisomerase IIα but not of Her-2/neu, and 48 samples (19.8%) displayed amplification for Her-2/neu but not for topoisomerase IIα. Correlation to the histologic type, the stage, or the grade could not be found. Only the amplification of topoisomerase IIα was associated with very poor outcome; survival of cases with amplification of Her-2/neu only was slightly lower than the mean overall survival (27.4 vs. 31.9 mo). Amplification of Her-2/neu and/or topoisomerase IIα is associated with poor overall survival. Amplification of topoisomerase IIα does not seem to be necessarily linked to Her-2/neu-amplification. However, independent determination of these 2 markers seems to be valuable for an individualized therapy of breast cancer patients.
authors.affiliation: Department of Obstetrics and Gynecology, Campus Innenstadt, Ludwig-Maximilians-University Munich, Munich, Germany. verena.engelstaedter@med.uni-muenchen
authors.forename: Verena
authors.initials: V
authors.lastname: Engelstaedter
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schiffers
authors.forename: Steffen
authors.initials: S
authors.lastname: Kahlert
authors.forename: Patrick
authors.initials: P
authors.lastname: Mainka
authors.forename: Jutta
authors.initials: J
authors.lastname: Engel
authors.forename: Thomas
authors.initials: T
authors.lastname: Kirchner
authors.forename: Joachim
authors.initials: J
authors.lastname: Diebold
authors.forename: Doris
authors.initials: D
authors.lastname: Mayr
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D056915:DNA Copy Number Variations; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D056726:Genetic Association Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human