Correlation between clinical outcome and growth factor pathway expression in osteogenic sarcoma.
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.
Abdeen
Ayesha
A
Department of Orthopaedic Surgery, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, New York, NY, USA.
Chou
Alexander J
AJ
Healey
John H
JH
Khanna
Chand
C
Osborne
Tanasa S
TS
Hewitt
Stephen M
SM
Kim
Mimi
M
Wang
Dan
D
Moody
Karen
K
Gorlick
Richard
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001859:Bone Neoplasms / Q000378:metabolism* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000378:metabolism* / Q000401:mortality; D040081:Protein Array Analysis; D015398:Signal Transduction; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A