Vascular endothelial growth factor and interleukin-8 are associated with poor prognosis in epithelial ovarian cancer patients
Introduction
The identification of prognostic factors that attempt to predict which patients are at high risk for poor outcome is one major advance in the management of ovarian carcinoma. Despite advances in chemotherapy, ovarian carcinoma remains the leading cause of death from gynecologic malignancy with mortality rates decreasing only marginally over the past few decades [1].
Tumor angiogenesis is a process necessary for solid tumor growth through establishment of the adequate blood supply for propagation of tumor cells and metastasis [2]. Among the tumor angiogenic factors, the main factors induced from tumor cells are basic fibroblast growth factor (basic FGF), vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8) [3].
Vascular endothelial growth factor (VEGF) is a disulfide-linked 34–45 kDa homodimeric glycoprotein expressed by a wide variety of solid tumors. It was reported first to have the ability to increase microvascular permeability [4]. Later, its capacity to act as a selective endothelial mitogen in addition to its ability to induce angiogenesis in vivo has been demonstrated [5]. Four subtypes of VEGF have been identified: VEGF206, 206 amino acids; VEGF189, deletion of exon 6′, 189 amino acids; VEGF165, deletion of exon 6, 6′, 165 amino acids; and VEGF121, deletion of exons 6, 6′, and 7, 121 amino acids. The smaller species are secreted and soluble, while the larger ones are secreted but remain bound to the cell and/or extracellular matrix, due to the addition in larger forms of basic sequences that bind more tightly to heparin and other polyanions [6].
Ovarian cancer has been proposed to be “a cytokine-propelled disease” based on the numerous cytokine receptors that are expressed in these tumors [7]. Interleukin-8 (IL-8) is a small (8 kDa) chemotactic cytokine mainly attracting and activating neutrophilic granulocytes, but it is also implicated in angiogenic events [8]. Local expression of IL-8 has been reported in several human tumor types, such as colorectal, breast, and prostate carcinomas [9], [10], [11].
The aim of the current investigation is to examine the clinical significance and the predictive value of VEGF overexpression as well as the frequency of IL-8 expression in epithelial ovarian cancer patients to acquire more information about possible role of these angiogenic factors in the biology of ovarian tumors.
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Subjects and methods
This study was conducted in the period from March 1999 to April 2002. The clinical specimens were obtained from the Obstetrics and Gynecology Department, Ain Shams University Hospitals. The laboratory work was carried out at the Oncology Diagnostic Unit (ODU), Medical Biochemistry Department, Ain Shams Faculty of Medicine.
Results
Vascular endothelial growth factor and IL-8 expression were assessed in benign and malignant ovarian tumors. The benign group included 20 patients (mean age, 37.1 ± 12.2; range, 20–60 years); the malignant group included 24 epithelial ovarian cancer patients (mean age, 43.5 ± 15.9; range, 21–65 years). Of the malignant group, 10 tumors were papillary serous adenocarcinoma, 7 were mucinous, and 7 were endometrioid tumors. All patients have been followed up for a total follow-up period of 36
Discussion
Newly developed capillary network formation from the original vessel is known as neovascularization. Generally, the turnover of capillary endothelial cells is extremely slow in, the order of months or years, physiologic neovascularization, whereas the turnover in the ovary and the endometrium is rapidly altered along with the ovarian cycle. In malignant transformation, the turnover becomes rapid, which could contribute to the acceleration of tumor growth [21].
In this study, it was demonstrated
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