BACKGROUND: Elevated ErbB2 expression and gene amplification have been shown to be associated with poor prognosis in many cancers. Recently, it has been demonstrated that overexpression of ErbB2 protein in osteosarcoma is associated with the presence of pulmonary metastasis and decreased survival. By contrast, a previous study showed that the expression of ErbB2 declines in individual osteosarcomas as they become metastatic. In the current study, the authors determined the relation between ErbB2 status and outcome in a large number of selected patients with high-grade osteosarcoma. METHODS: ErbB2 status was determined immunohistochemically in biopsy specimens of osteosarcoma of the extremities from 81 patients who were treated with surgery and chemotherapy. None of the patients had metastatic disease at presentation (Stage II), and all were followed-up for at least five years. The ErbB2 status was analyzed in relation to the lengths of event-free and overall survival. RESULTS: Of the 81 tumors examined, 51 (61%) demonstrated high levels of ErbB2 expression. The presence of increased levels of ErbB2 in osteosarcoma was significantly associated with the increased probability of event-free (72.2% v. 45.6% at 5 years, P = 0.03) and overall survival (79.7% v. 58.2% at 5 years, P = 0.03). Cox multivariate analysis showed that the risk of adverse events and death was increased substantially (rate ratio: 2.24 and 2.54; 95% confidence interval, 1.07-4.72 and 1.09-5.67, respectively) among patients with decreased levels of ErbB2 protein in tumor cells, as compared with patients who had increased levels of ErbB2 in tumor cells. CONCLUSIONS: In patients with high-grade osteosarcoma without metastatic disease at presentation and treated with surgery and chemotherapy, the presence of increased levels of ErbB2 in tumor cells is associated with a significantly increased probability of event-free and overall survival. Further data are needed before this marker can be used in making clinical decisions. Copyright 2002 American Cancer Society.
BACKGROUND: Elevated ErbB2 expression and gene amplification have been shown to be associated with poor prognosis in many cancers. Recently, it has been demonstrated that overexpression of ErbB2 protein in osteosarcoma is associated with the presence of pulmonary metastasis and decreased survival. By contrast, a previous study showed that the expression of ErbB2 declines in individual osteosarcomas as they become metastatic. In the current study, the authors determined the relation between ErbB2 status and outcome in a large number of selected patients with high-grade osteosarcoma. METHODS:ErbB2 status was determined immunohistochemically in biopsy specimens of osteosarcoma of the extremities from 81 patients who were treated with surgery and chemotherapy. None of the patients had metastatic disease at presentation (Stage II), and all were followed-up for at least five years. The ErbB2 status was analyzed in relation to the lengths of event-free and overall survival. RESULTS: Of the 81 tumors examined, 51 (61%) demonstrated high levels of ErbB2 expression. The presence of increased levels of ErbB2 in osteosarcoma was significantly associated with the increased probability of event-free (72.2% v. 45.6% at 5 years, P = 0.03) and overall survival (79.7% v. 58.2% at 5 years, P = 0.03). Cox multivariate analysis showed that the risk of adverse events and death was increased substantially (rate ratio: 2.24 and 2.54; 95% confidence interval, 1.07-4.72 and 1.09-5.67, respectively) among patients with decreased levels of ErbB2 protein in tumor cells, as compared with patients who had increased levels of ErbB2 in tumor cells. CONCLUSIONS: In patients with high-grade osteosarcoma without metastatic disease at presentation and treated with surgery and chemotherapy, the presence of increased levels of ErbB2 in tumor cells is associated with a significantly increased probability of event-free and overall survival. Further data are needed before this marker can be used in making clinical decisions. Copyright 2002 American Cancer Society.
Authors: David Ebb; Paul Meyers; Holcombe Grier; Mark Bernstein; Richard Gorlick; Steven E Lipshultz; Mark Krailo; Meenakshi Devidas; Donald A Barkauskas; Gene P Siegal; William Shay Ferguson; George Douglas Letson; Karen Marcus; Allen Goorin; Peter Beardsley; Neyssa Marina Journal: J Clin Oncol Date: 2012-06-04 Impact factor: 44.544
Authors: J S Whelan; R C Jinks; A McTiernan; M R Sydes; J M Hook; L Trani; B Uscinska; V Bramwell; I J Lewis; M A Nooij; M van Glabbeke; R J Grimer; P C W Hogendoorn; A H M Taminiau; H Gelderblom Journal: Ann Oncol Date: 2011-10-19 Impact factor: 32.976
Authors: Sarah Gorlick; Donald A Barkauskas; Mark Krailo; Sajida Piperdi; Rebecca Sowers; Jonathan Gill; David Geller; R Lor Randall; Katherine Janeway; Cindy Schwartz; Holcombe Grier; Paul A Meyers; Richard Gorlick; Mark Bernstein; Neyssa Marina Journal: Pediatr Blood Cancer Date: 2014-04-22 Impact factor: 3.167
Authors: Branden S Moriarity; George M Otto; Eric P Rahrmann; Susan K Rathe; Natalie K Wolf; Madison T Weg; Luke A Manlove; Rebecca S LaRue; Nuri A Temiz; Sam D Molyneux; Kwangmin Choi; Kevin J Holly; Aaron L Sarver; Milcah C Scott; Colleen L Forster; Jaime F Modiano; Chand Khanna; Stephen M Hewitt; Rama Khokha; Yi Yang; Richard Gorlick; Michael A Dyer; David A Largaespada Journal: Nat Genet Date: 2015-05-11 Impact factor: 38.330