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Correlation between clinical outcome and growth factor pathway expression in osteogenic sarcoma
Author(s) -
Abdeen Ayesha,
Chou Alexander J.,
Healey John H.,
Khanna Chand,
Osborne Tanasa S.,
Hewitt Stephen M.,
Kim Mimi,
Wang Dan,
Moody Karen,
Gorlick Richard
Publication year - 2009
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.24562
Subject(s) - vascular endothelial growth factor , protein kinase b , growth factor , cancer research , sarcoma , vascular endothelial growth factor a , platelet derived growth factor receptor , immunohistochemistry , medicine , tissue microarray , signal transduction , mapk/erk pathway , pathology , biology , receptor , microbiology and biotechnology , vegf receptors
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. Cancer 2009. Published 2009 by the American Cancer Society.