title: Amplification of HER-2/neu and topoisomerase IIalpha in primary and metastatic breast cancer.
abstract: Amplification of the HER-2/neu oncogene and amplification of the topoisomerase IIalpha gene are important determinators of the response to chemotherapy in advanced breast cancer. Assays of these genes are usually carried out using primary tumor samples, because biopsies from metastatic lesions are not usually taken. We studied the concordance of Her-2/neu and topoisomerase IIalpha amplification in primary breast tumors and their metastases by immunostaining and DNA in situ hybridization. HER-2/neu amplification, present in 28% of the primary tumors (n = 46), was always associated with amplification in its metastasis. Conversely, no metastases with HER-2/neu amplification were seen without amplification in the primary tumor. Topoisomerase IIalpha gene copy status (amplification/deletion/unaltered) remained generally unchanged in HER-2/neu-positive tumors, but in three cases, the predominant cell population in metastatic tissue was present only as a subpopulation in the primary tumor. We conclude that amplification of HER-2/neu measured in primary tumor reflects the status of metastases. Minor discrepancies between primary and metastatic tumors in topoisomerase IIalpha gene copy status may reflect evolvement of the amplicon structure in successive cell divisions.
authors.affiliation: Laboratory of Cancer Genetics, Institute of Medical Technology, Tampere University and Tampere University Hospital, FIN-33014 Tampere, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Tanner
authors.forename: P
authors.initials: P
authors.lastname: Järvinen
authors.forename: J
authors.initials: J
authors.lastname: Isola
mesh_terms: D000951:Antigens, Neoplasm; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004250:DNA Topoisomerases, Type II / Q000032:analysis / Q000235:genetics*; D004268:DNA-Binding Proteins; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics*
chemical_list: D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D018719:Erb-b2 Receptor Tyrosine Kinases