title: Analysis of interleukin (IL)-8 expression in human astrocytomas: associations with IL-6, cyclooxygenase-2, vascular endothelial growth factor, and microvessel morphometry.
abstract: Malignant astrocytomas are highly vascular neoplasms with potent angiogenic activity. The present study aimed to investigate peripheral and local expression of interleukin (IL)-8 in astrocytomas with possible associations to IL-6, cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) expression, and microvessel morphometry. IL-6- and IL-8-secreting peripheral blood monocytes (PBMCs) were evaluated in 17 glioblastoma (WHO grade IV), 5 anaplastic astrocytoma (WHO grade III), and 6 diffuse astrocytoma patients (WHO grade II), in parallel with 23 healthy controls using enzyme-linked immunosorbent spot (ELISPOT) assay. The IL-8 expression was assessed immunohistochemically in patients' tumor tissue sections and correlated with the expression of COX-2, VEGF, IL-6, and microvessel morphometry (assessed using CD34 antibody). Eighteen cases were also stained for CD31 and used as an additional vessel marker to validate our results regarding microvessel morphometry. IL-6 and IL-8 were highly secreted in the PBMCs of glioma patients compared with controls (p = 0.0001, p < 0.0001, respectively), with a positive correlation between IL-8 expression and secretion levels (p = 0.001). IL-8 immunoreactivity was detected in malignant cells or macrophages in perivascular areas and in pseudopalisading cells around necrosis and was positively correlated with histological grade (p = 0.0175) and tumor necrosis (p = 0.0793). IL-6 and IL-8 expression levels were positively correlated (p = 0.0036) and associated with COX-2 and VEGF expression (IL-6: p = 0.0133, p = 0.065; IL-8: p = 0.0139, p = 0.0101), but not with microvessel morphometry, by either CD31 or CD34. The coordinate expression and topographical relationship of IL-6, IL-8, COX-2, and VEGF in the same tumor areas (e.g., perinecrotic areas) attest to their intimate liaison in terms of cancer-induced angiogenesis, which is probably secondary to the induction of multiple interdependent molecular pathways. Moreover, our study seems to be the first attempt to link IL-8 expression by tumor cells with histological grade, implicating its potent role in gliomagenesis.
authors.affiliation: Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Laiko Hospital, Athens 11527, Greece.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Samaras
authors.forename: Christina
authors.initials: C
authors.lastname: Piperi
authors.forename: Georgia
authors.initials: G
authors.lastname: Levidou
authors.forename: Athanasios
authors.initials: A
authors.lastname: Zisakis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kavantzas
authors.forename: Marios S
authors.initials: MS
authors.lastname: Themistocleous
authors.forename: Efstathios I
authors.initials: EI
authors.lastname: Boviatsis
authors.forename: Calypso
authors.initials: C
authors.lastname: Barbatis
authors.forename: Robert W
authors.initials: RW
authors.lastname: Lea
authors.forename: Anastasios
authors.initials: A
authors.lastname: Kalofoutis
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou