title: Expression of HER2/neu is uncommon in human neuroblastic tumors and is unrelated to tumor progression.
abstract: Neuroblastic tumors (NT) are the most frequently occurring extracranial solid tumors during childhood. The overall 5-year survival is approximately 20% for patients with metastatic disease. Novel treatments are therefore intensively sought and tumor-targeted immuno- and chemotherapy appear promising. The HER2/neu oncogene, which is highly homologous to the EGF receptor, was initially isolated from rat neuroblastoma cells. HER2/neu over-expression is frequently detected in breast tumors and constitutes an important unfavorable prognostic factor. HER2/neu is a suitable target for antibody-based immunotherapy, as demonstrated by the clinical efficacy of the Herceptin monoclonal antibody (mAb), which reacts with its extracellular domain. Expression of HER2/neu has also been reported to be a negative prognostic factor in a small survey of NT tumors. Here, we have investigated HER2/neu expression in 14 human and 2 murine neuroblastoma (NB) cell lines by flow cytometric analysis and in 93 NT by means of a certified immunohistochemical system. HER2/neu over-expression was found in 2 human cell lines and 11 tumors (14% for both types of samples). No significant association was found between HER2/neu expression and stage, age, sex, ploidy, histological type or subtype. Moreover, log rank test indicated that overall and event-free survival was not significantly different in HER2/neu positive and negative patients. These data suggest that HER2/neu should not be considered as a relevant prognostic factor in NT, and that HER2/neu-based immunotherapy may be feasible only in a minority of NT patients.
authors.affiliation: Pathology Department, Istituto G Gaslini, Largo Gaslini 5, 16148 Genoa, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Gambini
authors.forename: Angela Rita
authors.initials: AR
authors.lastname: Sementa
authors.forename: Luca
authors.initials: L
authors.lastname: Boni
authors.forename: Carla Enrica
authors.initials: CE
authors.lastname: Marino
authors.forename: Michela
authors.initials: M
authors.lastname: Croce
authors.forename: Francesca
authors.initials: F
authors.lastname: Negri
authors.forename: Vito
authors.initials: V
authors.lastname: Pistoia
authors.forename: Silvano
authors.initials: S
authors.lastname: Ferrini
authors.forename: Maria Valeria
authors.initials: MV
authors.lastname: Corrias
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D009447:Neuroblastoma / Q000737:chemistry* / Q000473:pathology / Q000628:therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D018719:Erb-b2 Receptor Tyrosine Kinases