European Journal of Obstetrics & Gynecology and Reproductive Biology
The impact of plasma fibrinogen levels on patients with vulvar cancer☆
Introduction
Fibrinogen, a 340 kD dimeric protein, is produced mainly by hepatocytes, tumor cells [1] and inflammation-mediating cells such as epithelial cells [2], and plays a pivotal role in haemostatic balance [3]. After cleavage and activation of fibrinogen by thrombin, the subsequently formed fibrin monomers become a structural meshwork that consolidates an initial platelet plug into a solid haemostatic clot [3].
Fibrinogen is one of several acute phase reactant proteins rising during systemic inflammation and tissue injury [4]. Furthermore, hyperfibrinogenemia reflects a state of hypercoagulation and thrombocytosis, which is known to be associated with malignant growth [5], [6]. The functional relationship between inflammation and neoplastic process concerning proliferation, survival, migration, invasion and metastasis of tumor cells is widely accepted [7], [8].
Recent studies in humans have indicated a correlation between plasma fibrinogen levels and tumor progression in patients with gastric cancer [9], [10], [11], esophageal cancer [12], non-small cell lung cancer [13], ovarian cancer [14], cervical cancer [15] and endometrial cancer [16].
In vulvar cancer, only a few serum biomarkers such as C-reactive protein (CRP) [17] and immunohistochemically detected CD44 [18] have been shown to correlate with tumor stage and lymph node involvement. Concerning prognosis, serum levels of carcinoembryonic antigen [19], urinary beta core fragment of human chorionic gonadotrophin [20], and squamous cell carcinoma (SCC) antigen [19], [21] have been described as valuable tools for evaluating the prognosis of affected patients.
The aim of the present study was to investigate the association between pretreatment plasma fibrinogen levels and clinico-pathological parameters in patients with vulvar cancer, and to assess their value as a prognostic parameter.
Section snippets
Patients
In the present retrospective study 120 consecutive patients with invasive squamous cell vulvar cancer, treated at the Department of Obstetrics and Gynecology, Medical University of Vienna, between December 1995 and June 2008, were enrolled. Clinical data were extracted from patient files. We excluded cases of vulvar melanoma, basal cell cancer and cancer of the Bartholin gland. Patients who had any other acute or chronic inflammatory disease were excluded from the study.
Clinical management
Diagnosis of vulvar
Results
Patients’ characteristics are given in Table 1. The mean (SD) pretreatment plasma fibrinogen level was 413.2 (107.9) mg/dl. Median follow up time was 12.6 months (range, 0–147.6 months). Plasma fibrinogen levels broken down by clinico-pathological parameters are given in Table 2. Elevated plasma fibrinogen levels were associated with advanced tumor stage, lymph node involvement and higher histological grade, but not with patients’ age (Table 2).
Tumor stage, lymph node involvement, histological
Comment
An important role of inflammation in tumor formation and progression has previously been reported [7], [8]. Fibrinogen-related products, mostly cross-linked fibrin, have been found in solid tumors in experimental animals and humans, suggesting an influence of fibrinogen on tumor stroma formation [4], [24], [25], [26]. Although plasma fibrinogen levels have been investigated in several malignancies, such as gastric cancer [9], [10], [11], esophageal cancer [12], non-small cell lung cancer [13],
Conflict of interest statement
No conflict of interest has to be stated for any of the participating authors.
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The conduction of the study took place at the Medical University of Vienna, Austria.