The impact of plasma fibrinogen levels on patients with vulvar cancer

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Abstract

Objective

To investigate the association between plasma fibrinogen levels and clinico-pathological parameters of patients with vulvar cancer and to determine their value as prognostic parameters.

Study design

In this retrospective study, we evaluated pretreatment plasma fibrinogen levels in 120 patients with invasive squamous cell vulvar cancer and correlated them with clinico-pathological parameters and patients’ survival.

Results

Pretreatment plasma fibrinogen levels were directly associated with tumor stage (pT1a vs. pT1b vs. pT2 vs. pT3-4, p = 0.001), lymph node involvement (pN0 vs. pN1, p = 0.04), and histological grade (G1 vs. G2 vs. G3, p = 0.03), but not with patients’ age (≤70 years vs. >70 years, p = 0.6). In a multivariate survival analysis, tumor stage (p = 0.006/p = 0.02) and lymph node involvement (p < 0.001/p < 0.001), but neither histological grade (p = 0.2/p = 0.9) nor plasma fibrinogen levels (p = 0.6/p = 0.6) were associated with disease-free and overall survival, respectively. In a multivariate analysis, patient's age (≤70 years vs. >70 years) was associated with overall survival (p = 0.03) but not with disease-free survival (p = 0.1).

Conclusion

Pretreatment plasma fibrinogen levels were directly associated with tumor stage, lymph node involvement and histological grade. Although we could demonstrate a prognostic value of pretreatment plasma fibrinogen levels on survival, we were unable to establish fibrinogen as an independent prognostic parameter in 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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