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Angiogenesis and expression of PDGF ‐ C , VEGF , CD 105 and HIF ‐1α in human glioblastoma
Author(s) -
Clara Carlos Afonso,
Marie Suely K.N.,
Almeida José Reynaldo Walther,
Wakamatsu Alda,
ObaShinjo Sueli Mieko,
Uno Miyuki,
Neville Munro,
Rosemberg Sérgio
Publication year - 2014
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/neup.12111
Subject(s) - angiogenesis , platelet derived growth factor receptor , immunohistochemistry , vascular endothelial growth factor , cancer research , growth factor , pathology , medicine , chemistry , biology , vegf receptors , receptor
Glioblastoma ( GBM ), the most frequent and aggressive brain tumor, is characterized by marked angiogenesis directly related to invasiveness and poor prognosis. Hypoxia is considered to be an important stimulus for angiogenesis by inducing hypoxia‐inducible factor 1‐alpha ( HIF ‐1α) overexpression that activates platelet‐derived growth factor ( PDGF ) and VEGF . The aim of this study is to analyze the expression of PDGF ‐ C , VEGF in endothelial and tumor cells of GBM and their relation to HIF ‐1α expression. Two hundred and eight GBM cases were studied by tissue microarray immunohistochemical preparation. Expression of HIF ‐1α, VEGF and PDGF ‐ C was observed in 184 (88.5%), 131 (63%) and 160 (76.9%) tumor cases, respectively. The numbers of vessels were quantified by CD 34, PDGF ‐ C , VEGF and CD 105 staining, and were in median 20, 16, 5 and 6, respectively. The GBMs that showed positive or negative expression for HIF ‐1α showed a median vascular density of 30 and 14, respectively, for CD 34 ( P < 0.015). Positive expression for HIF ‐1α was correlated with VEGF and PDGF ‐ C expression in tumors ( P < 0.001). There was a significant correlation between VEGF and PDGF ‐ C expression in the cytoplasm of GBM tumor cells ( P < 0.0001). We showed that VEGF expression in tumor cells was correlated with its expression in blood vessels ( P < 0.0001). Endothelial cells with PDGF ‐ C and VEGF positive expression were also positive for CD 105 and their nuclei for K i‐67, confirming the neoangiogenic and proliferative influence of VEGF and PDGF ‐ C . VEGF nuclear staining in tumor cells ( P = 0.002) as well as nuclear staining for HIF ‐1α and VEGF ( P = 0.005) correlated with survival. In summary, our present findings of the concomitant upregulation of PDGF ‐ C with VEGF in GBM tumor cells and vessels further reinforce the benefit of using combined anti‐angiogenic approaches to potentially improve the therapeutic response for GBM .