Τίτλος:
Prognostic significance of IL-8-STAT-3 pathway in astrocytomas: Correlation with IL-6, VEGF and microvessel morphometry
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Piperi, C.
Samaras, V.
Levidou, G.
Kavantzas, N.
Boviatsis, E.
Petraki, K.
Grivas, A.
Barbatis, C.
Varsos, V.
Patsouris, E.
Korkolopoulou, P.
Λέξεις-κλειδιά:
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
DOI:
10.1016/j.cyto.2011.05.012
