TY - JOUR
TI - Prognostic significance of IL-8-STAT-3 pathway in astrocytomas: Correlation with IL-6, VEGF and microvessel morphometry
AU - Piperi, C.
AU - Samaras, V.
AU - Levidou, G.
AU - Kavantzas, N.
AU - Boviatsis, E.
AU - Petraki, K.
AU - Grivas, A.
AU - Barbatis, C.
AU - Varsos, V.
AU - Patsouris, E.
AU - Korkolopoulou, P.
JO - Cytokine
PY - 2011
VL - 55
TODO - 3
SP - 387-395
PB - 
SN - 1043-4666, 1096-0023
TODO - 10.1016/j.cyto.2011.05.012
TODO - interleukin 6;  interleukin 8;  STAT3 protein;  vasculotropin, adult;  aged;  article;  astrocytoma;  cancer grading;  cancer growth;  cancer survival;  cell infiltration;  clinical feature;  controlled study;  disease association;  disease severity;  female;  gene overexpression;  human;  human tissue;  immunohistochemistry;  immunoreactivity;  major clinical study;  male;  microvasculature;  predictive value;  priority journal;  prognosis;  protein expression;  protein function;  protein localization;  protein targeting;  signal transduction, Adult;  Aged;  Aged, 80 and over;  Astrocytoma;  Brain Neoplasms;  Cohort Studies;  Female;  Humans;  Immunotherapy;  Interleukin-6;  Interleukin-8;  Male;  Microvessels;  Middle Aged;  Neovascularization, Pathologic;  Prognosis;  Signal Transduction;  STAT3 Transcription Factor;  Tumor Markers, Biological;  Vascular Endothelial Growth Factor A;  Vascular Neoplasms
TODO - Malignant astrocytomas are highly vascular neoplasms characterized by a potent angiogenic and immunosuppressive phenotype. Th2-cytokines (IL-6/IL-8) are implicated as major regulators of glioma cell growth and invasiveness. STAT-3, a downstream transducer of cytokine signaling is positively associated with tumor angiogenesis. The present study aimed to investigate the expression of IL-8 and p-STAT-3 in 97 diffusely infiltrating astrocytomas of various grades, in relation to IL-6, VEGF, clinicopathological features, microvascular characteristics and patients' survival. IL-8 expression was localized in neoplastic cells, being associated with p-STAT-3 (p = 0.0013), IL-6 (p = 0.0004) and VEGF (p< 0.0001) around areas of necrosis as well as in perivascular inflammatory and endothelial cells. All the molecules under study correlated with tumor grade and degree of necrosis (p< 0.05, respectively). p-STAT-3, IL-8 and VEGF expression was positively associated with microvessel density (p = 0.0491, p< 0.0001 and p = 0.0118, respectively).Univariate analysis indicated that overexpression of IL-8 and IL-6 adversely affected survival in the entire cohort whereas increased p-STAT-3 expression was predictive of improved survival in high grade (III/IV) astrocytomas (p = 0.0032). In multivariate analysis only IL-8 expression (p = 0.043) retained its significance. The prognostic significance of IL-8 expression and its correlation with p-STAT-3 and VEGF implicates this novel signaling pathway in astroglial tumors progression providing new targets for effective immunotherapy. © 2011 Elsevier Ltd.
ER -