Correlation between clinical outcome and growth factor pathway expression in osteogenic sarcoma Journal Article


Authors: Abdeen, A.; Chou, A. J.; Healey, J. H.; Khanna, C.; Osborne, T. S.; Hewitt, S. M.; Kim, M.; Wang, D.; Moody, K.; Gorlick, R.
Article Title: Correlation between clinical outcome and growth factor pathway expression in osteogenic sarcoma
Abstract: 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.
Keywords: immunohistochemistry; osteosarcoma; signal transduction; survival; epidermal growth factor; mitogen activated protein kinase; platelet derived growth factor; protein kinase b; s6 kinase; somatomedin; vasculotropin; vasculotropin b; vasculotropin receptor 3; adolescent; adult; cancer chemotherapy; cancer survival; child; clinical article; controlled study; event free survival; human tissue; preschool child; protein expression; protein phosphorylation; school child; treatment outcome; treatment response; aged; aged, 80 and over; bone neoplasms; child, preschool; disease-free survival; intercellular signaling peptides and proteins; middle aged; protein array analysis; survival analysis; vascular endothelial growth factor a
Journal Title: Cancer
Volume: 115
Issue: 22
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2009-11-15
Start Page: 5243
End Page: 5250
Language: English
DOI: 10.1002/cncr.24562
PUBMED: 19670450
PROVIDER: scopus
PMCID: PMC7251638
DOI/URL:
Notes: --- - "Cited By (since 1996): 4" - "Export Date: 30 November 2010" - "CODEN: CANCA" - "Source: Scopus"
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  1. Ayesha Abdeen
    4 Abdeen
  2. Alexander Ja-Ho Chou
    58 Chou
  3. John H Healey
    550 Healey