Prognostic and therapeutic relevance of HER2 expression in osteosarcoma and Ewing's sarcoma.
Expression of HER2 was evaluated by immunohistochemical techniques in 84 osteosarcoma (OS) and 113 Ewing's sarcoma (ES) paraffin-embedded tumour biopsies. HER2 gene status was also assessed in a panel of cell lines as well as in vitro efficacy of trastuzumab (a humanised antibody directed against HER2) as single agent or in combination with the insulin-like growth factor I receptor (IGF-IR) IR3 antibody. Overexpression of HER2 was present in 32% of OS and 16% of ES and was significantly associated with the increased expression of P-glycoprotein, a surface molecule responsible for multidrug resistance. Event-free survival analyses revealed a prognostic value for HER2 and/or P-glycoprotein expression in OS, but not in ES. However, despite its prognostic relevance, no therapeutic effectiveness was observed pre-clinically for trastuzumab-driven therapy, in both OS or ES cell lines, unless the antibody was associated with anti-IGF-IR targeting strategies. Therefore, the therapeutic potential of trastuzumab in these neoplasms may be better exploited in combined treatments with anti-IGF-IR approaches.
Scotlandi
Katia
K
Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy. katia.scotlandi@ior.it
Manara
Maria C
MC
Hattinger
Claudia M
CM
Benini
Stefania
S
Perdichizzi
Stefania
S
Pasello
Michela
M
Bacci
Gaetano
G
Zanella
Licciana
L
Bertoni
Franco
F
Picci
Piero
P
Serra
Massimo
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D018739:Oncogene Proteins v-erbB / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D012512:Sarcoma, Ewing / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D000068878:Trastuzumab; D016896:Treatment Outcome
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018739:Oncogene Proteins v-erbB; D017526:Receptor, IGF Type 1; D000068878:Trastuzumab