title: Her-2/neu expression in osteosarcoma increases risk of lung metastasis and can be associated with gene amplification.
abstract: The purpose of this study was to investigate whether Her-2/neu expression at diagnosis of osteosarcoma could provide biologic and prognostic information that predicts the risk of pulmonary metastases and outcome. Human epidermal growth factor (Her-2/neu) expression in 25 initial pretreatment osteosarcoma biopsies and 12 posttreatment pulmonary metastatic osteosarcoma resection specimens was assessed by standard immunohistochemical techniques on formalin-fixed paraffin-embedded tissue. As a screening analysis to determine if gene amplification may be a mechanism for increased Her-2/neu expression, FISH analysis was conducted on seven Her-2/neu immunostain-positive samples and five Her-2/neu immunostain-negative samples. Cytoplasmic Her-2/neu reactivity was identified in 11/25 (44%) of primary tumors and in 7/12 (58%) resection specimens from pulmonary metastases. Cytoplasmic Her-2/neu expression was associated with shorter overall metastasis-free survival. Her-2/neu gene amplification was identified by FISH analysis in six of the seven immunostain-positive samples but was also identified in two of the five immunostain-negative samples. Her-2/neu expression in patients with osteosarcoma is associated with an increased risk of metastasis and may define a subset of patients with a more aggressive tumor phenotype. Her-2/neu gene amplification may provide a mechanism for Her-2/neu overexpression in certain cases of osteosarcoma. Whether Her-2/neu expression influences outcome needs to be examined further in a prospective fashion. The hope is that Her-2/neu expression will identify patients who may benefit from the addition of directed biologic therapy.
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, UT, USA.
authors.forename: Holly
authors.initials: H
authors.lastname: Zhou
authors.forename: R Lor
authors.initials: RL
authors.lastname: Randall
authors.forename: Arthur R
authors.initials: AR
authors.lastname: Brothman
authors.forename: Teresa
authors.initials: T
authors.lastname: Maxwell
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Coffin
authors.forename: Robert E
authors.initials: RE
authors.lastname: Goldsby
mesh_terms: D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D002648:Child; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000378:metabolism* / Q000556:secondary; D008297:Male; D012516:Osteosarcoma / Q000378:metabolism* / Q000556:secondary; D010865:Pilot Projects; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D015996:Survival Rate; D015854:Up-Regulation
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases