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

Ayesha Abdeen, Alexander Ja-Ho Chou, John H. Healey, Chand Khanna, Tanasa S. Osborne, Stephen M. Hewitt, Mimi Kim, Dan Wang, Karen Moody, Richard Gorlick

Research output: Contribution to journalArticle

54 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)5243-5250
Number of pages8
JournalCancer
Volume115
Issue number22
DOIs
StatePublished - Nov 15 2009

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Osteosarcoma
Intercellular Signaling Peptides and Proteins
Proteins
Mitogen-Activated Protein Kinases
Endothelial Growth Factors
Ribosomal Protein S6 Kinases
Platelet-Derived Growth Factor
Somatomedins
Protein Kinases
Vascular Endothelial Growth Factor A
Disease-Free Survival
Survival
Vascular Endothelial Growth Factor B
Biomarkers
Vascular Endothelial Growth Factor Receptor-3
Staining and Labeling
Drug Therapy
Vascular Endothelial Growth Factor Receptor
Critical Pathways
Thymoma

Keywords

  • Immunohistochemistry
  • Osteosarcoma
  • Signal transduction
  • Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Abdeen, A., Chou, A. J-H., Healey, J. H., Khanna, C., Osborne, T. S., Hewitt, S. M., ... Gorlick, R. (2009). Correlation between clinical outcome and growth factor pathway expression in osteogenic sarcoma. Cancer, 115(22), 5243-5250. https://doi.org/10.1002/cncr.24562

Correlation between clinical outcome and growth factor pathway expression in osteogenic sarcoma. / Abdeen, Ayesha; Chou, Alexander Ja-Ho; Healey, John H.; Khanna, Chand; Osborne, Tanasa S.; Hewitt, Stephen M.; Kim, Mimi; Wang, Dan; Moody, Karen; Gorlick, Richard.

In: Cancer, Vol. 115, No. 22, 15.11.2009, p. 5243-5250.

Research output: Contribution to journalArticle

Abdeen, A, Chou, AJ-H, Healey, JH, Khanna, C, Osborne, TS, Hewitt, SM, Kim, M, Wang, D, Moody, K & Gorlick, R 2009, 'Correlation between clinical outcome and growth factor pathway expression in osteogenic sarcoma', Cancer, vol. 115, no. 22, pp. 5243-5250. https://doi.org/10.1002/cncr.24562
Abdeen, Ayesha ; Chou, Alexander Ja-Ho ; Healey, John H. ; Khanna, Chand ; Osborne, Tanasa S. ; Hewitt, Stephen M. ; Kim, Mimi ; Wang, Dan ; Moody, Karen ; Gorlick, Richard. / Correlation between clinical outcome and growth factor pathway expression in osteogenic sarcoma. In: Cancer. 2009 ; Vol. 115, No. 22. pp. 5243-5250.
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AU - Chou, Alexander Ja-Ho

AU - Healey, John H.

AU - Khanna, Chand

AU - Osborne, Tanasa S.

AU - Hewitt, Stephen M.

AU - Kim, Mimi

AU - Wang, Dan

AU - Moody, Karen

AU - Gorlick, Richard

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N2 - 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.

AB - 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.

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