BACKGROUND: Multiple cell-signaling ligands and receptors-including vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), endothelial growth factor (EGF), v-akt murine thymoma viral oncogene homolog (AKT), platelet-derived growth factor (PDGF), mitogen-activated protein kinase (MAPK), and 70-kilodalton (kD) protein S6 kinase (p70S6 kinase)-reportedly are variably expressed in osteogenic sarcoma. Expression of these proteins may have future implications for prognostication and targeted therapy. The objective of the current study was to determine the relation between clinical outcome and the expression of these proteins. METHODS: A paraffin-embedded microarray of 48 human osteogenic sarcoma tissue specimens was stained with the antibodies against VEGF, IGF, EGF, AKT, PDGF, MAPK, and p70S6 kinase. Staining for each protein included the total protein and, when applicable, the phosphorylated version of the protein. Immunohistochemical staining was then correlated with patient survival (overall survival [OS] and event-free survival [EFS]), histologic response to chemotherapy, and serum markers. RESULTS: There was a negative correlation between VEGF receptor 3 (VEGF-R3) and both OS and EFS. VEGF-B was correlated with a poor histologic response to chemotherapy. Serum markers were not correlated with any specific proteins. When using a P value of .05, multiple correlations were observed between proteins of various pathways. CONCLUSIONS: The current results suggested that the VEGF pathway is a critical signaling pathway in osteogenic sarcoma. These data have identified specific proteins within these pathways toward which future investigations should be directed to further clarify their prognostic potential.
BACKGROUND: Multiple cell-signaling ligands and receptors-including vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), endothelial growth factor (EGF), v-aktmurinethymoma viral oncogene homolog (AKT), platelet-derived growth factor (PDGF), mitogen-activated protein kinase (MAPK), and 70-kilodalton (kD) protein S6 kinase (p70S6 kinase)-reportedly are variably expressed in osteogenic sarcoma. Expression of these proteins may have future implications for prognostication and targeted therapy. The objective of the current study was to determine the relation between clinical outcome and the expression of these proteins. METHODS: A paraffin-embedded microarray of 48 humanosteogenic sarcoma tissue specimens was stained with the antibodies against VEGF, IGF, EGF, AKT, PDGF, MAPK, and p70S6 kinase. Staining for each protein included the total protein and, when applicable, the phosphorylated version of the protein. Immunohistochemical staining was then correlated with patient survival (overall survival [OS] and event-free survival [EFS]), histologic response to chemotherapy, and serum markers. RESULTS: There was a negative correlation between VEGF receptor 3 (VEGF-R3) and both OS and EFS. VEGF-B was correlated with a poor histologic response to chemotherapy. Serum markers were not correlated with any specific proteins. When using a P value of .05, multiple correlations were observed between proteins of various pathways. CONCLUSIONS: The current results suggested that the VEGF pathway is a critical signaling pathway in osteogenic sarcoma. These data have identified specific proteins within these pathways toward which future investigations should be directed to further clarify their prognostic potential.
Authors: Y H Lee; T Tokunaga; Y Oshika; R Suto; K Yanagisawa; M Tomisawa; H Fukuda; H Nakano; S Abe; A Tateishi; H Kijima; H Yamazaki; N Tamaoki; Y Ueyama; M Nakamura Journal: Eur J Cancer Date: 1999-07 Impact factor: 9.162
Authors: M Kaya; T Wada; T Akatsuka; S Kawaguchi; S Nagoya; M Shindoh; F Higashino; F Mezawa; F Okada; S Ishii Journal: Clin Cancer Res Date: 2000-02 Impact factor: 12.531
Authors: Bang H Hoang; Jonathan P Dyke; Jason A Koutcher; Andrew G Huvos; Hiroo Mizobuchi; Beth Anne Mazza; Richard Gorlick; John H Healey Journal: Clin Orthop Relat Res Date: 2004-09 Impact factor: 4.176
Authors: Paul A Meyers; Cindy L Schwartz; Mark D Krailo; John H Healey; Mark L Bernstein; Donna Betcher; William S Ferguson; Mark C Gebhardt; Allen M Goorin; Michael Harris; Eugenie Kleinerman; Michael P Link; Helen Nadel; Michael Nieder; Gene P Siegal; Michael A Weiner; Robert J Wells; Richard B Womer; Holcombe E Grier Journal: J Clin Oncol Date: 2008-02-01 Impact factor: 44.544
Authors: P A Meyers; G Heller; J Healey; A Huvos; J Lane; R Marcove; A Applewhite; V Vlamis; G Rosen Journal: J Clin Oncol Date: 1992-01 Impact factor: 44.544
Authors: Chand Khanna; Jennifer Prehn; David Hayden; Ryan D Cassaday; Jana Caylor; Shevin Jacob; Seuli M Bose; Sung-Hyeok Hong; Stephen M Hewitt; Lee J Helman Journal: Clin Cancer Res Date: 2002-07 Impact factor: 12.531
Authors: Scott C Borinstein; Donald A Barkauskas; Mark Bernstein; Allen Goorin; Richard Gorlick; Mark Krailo; Cindy L Schwartz; Leonard H Wexler; Jeffrey A Toretsky Journal: Pediatr Blood Cancer Date: 2013-10-31 Impact factor: 3.167
Authors: Tanasa S Osborne; Ling Ren; John H Healey; Lauren Q Shapiro; Alexander J Chou; Richard G Gorlick; Stephen M Hewitt; Chand Khanna Journal: J Pediatr Hematol Oncol Date: 2011-10 Impact factor: 1.289
Authors: Dhong Hyun Lee; Nils H Thoennissen; Catherine Goff; Gabriela B Iwanski; Charles Forscher; Ngan B Doan; Jonathan W Said; H Phillip Koeffler Journal: Cancer Lett Date: 2011-03-26 Impact factor: 8.679