Preoperative serum vascular endothelial growth factor as a prognostic parameter in ovarian cancer

Abstract

Objective.

Serum vascular endothelial growth factor (VEGF) levels have been shown to be associated with an adverse outcome in patients with ovarian cancer. We studied the clinical value of serum VEGF as an independent prognostic parameter.

Methods.

In the present study, we ascertained preoperative serum VEGF in a series of 314 patients with ovarian cancer: 45 new cases and 269 from four previously published studies. Serum VEGF was evaluated prior to primary surgery, results were correlated with clinical data.

Results.

Median serum VEGF was 407 (238–746) pg/mL. In a univariate Kaplan–Meier analysis, FIGO stage, residual tumor mass, tumor grade, patients' age, serum CA 125, and preoperative serum VEGF were associated with overall survival. In a multivariate Cox regression model, higher FIGO stage, presence of residual tumor mass after primary surgery, and higher serum VEGF were independently associated with a shortened overall survival. Planned subgroup analysis was performed for patients with ovarian cancer FIGO stage I. In a multivariate Cox regression model, higher tumor grade and higher serum VEGF were the only independent prognosticators for overall survival. Patients with FIGO stage I ovarian cancer and a serum VEGF ≥ 380 pg/mL had an 8-fold increased risk for experiencing cancer-related death.

Conclusion.

Serum VEGF is an independent prognostic parameter in patients with all stages of ovarian cancer.

Introduction

Tumor stage and residual tumor mass at primary cytoreductive surgery have been shown to most reliably predict outcome in patients with ovarian cancer [1]. Clinical decision making with respect to adjuvant therapy is largely based on FIGO stage and tumor grade, especially in early stage disease. Recently, the necessity of adjuvant chemotherapy in early stage ovarian cancer has been questioned [2]. Therefore, the need for additional prognostic parameters seems obvious. In contrast to other malignancies [3], [4], few experimental prognostic parameters have proven any clinical value in ovarian cancer.

Angiogenesis has been established as a basic feature of tumor development, growth, and spread beyond regional borders [5], [6]. Vascular endothelial growth factor (VEGF), which can be seen as the most prominent pro-angiogenic molecule, has been shown to parallel selective steps of tumor growth and the development of metastases [7], [8]. VEGF is a dimeric glycoprotein with four splice variants consisting of 121, 165, 189, and 206 amino acid residues, expressing almost identical biologic activities by binding to specific Class III receptor tyrosine kinases, that is, flt-1 and KDR [9].

Experimental in vitro and in vivo studies have shown that VEGF is crucially involved in various steps of ovarian carcinogenesis [10], [11], [12]. Recently, immunohistochemically detected VEGF was shown to be associated with a dismal prognosis of ovarian cancer [13], [14]. With respect to serum VEGF in ovarian cancer, a number of studies have been published to date in the English literature. Seven of those studies also reported on the prognostic impact of serum VEGF [15], [16], [17], [18], [19], [20], [21]. As the number of patients included in these studies were relatively low, the clinical value of preoperative serum VEGF was not adequately assessed. Therefore, we contacted all corresponding authors, four of which responded and provided the original data of their studies. In addition, we analyzed 45 new cases of ovarian cancer of our own institution adding up to a total of 314 cases.

Based on the promising previously published data and the need to predict prognosis of affected patients more precisely in order to tailor adjuvant therapy, we evaluated the clinical value of serum VEGF as a prognostic parameter in a large series of patients with ovarian cancer. Specifically, we also sought to establish the prognostic impact of serum VEGF in early stage disease [22].