Abstract
ObjectiveThe plasminogen activator system (PAS) and vascular endothelial growth factor (VEGF) are important in the carcinogenesis and play a key role in cancer invasion and mediating metastasis of carcinomas. The aim of the study was to evaluate the correlation of serum levels of VEGF and components of the PAS with clinicopathological risk factors and outcome in patients with endometrial cancer (EC).MethodsPreoperative blood was collected from 173 patients treated for EC between 1999 and 2009. Serum concentrations of VEGF, urokinase plasminogen activator (uPA) tissue plasminogen activator (tPA), plasminogen activator inhibitor type-1 (PAI-1) and -2 (PAI-2) were assessed by enzyme-linked immunosorbent assays (ELISA).ResultsSerum levels of VEGF and components of the PAS were significantly associated with stage of the disease, tumor histology, tumor grade, myometrial invasion (MI), presence of lymphovascular space invasion (LVSI) and lymph node metastases (LNM). Preoperative serum levels of PAI-1 and -2 and tPA were higher in patients who experienced a recurrence than in patients who remained disease free (p < 0.01). PAI-1 and -2 and tPA were significantly independent prognostic factors for DFS with a HR of 3.85 (95% CI 1.84–8.07), 3.90 (95% CI 1.75–8.66) and 2.53 (95% CI 1.16–5.55), respectively. PAI-1 and tPA turned out to be independent prognostic factors for OS, with a HR of 2.09 (95% CI 1.08–4.05) and 2.16 (95% CI 1.06–4.44), respectively.ConclusionSerum levels of VEGF and components of the PAS at primary diagnosis were associated with well-known clinicopathological risk factors such as; FIGO stage, tumor histology, tumor grade, MI, LVSI and LNM. High concentrations of PAI-1 and-2 and tPA are independent factors for poor prognosis in patients with endometrial cancer.
Highlights
Endometrial cancer (EC) causes early symptoms such as postmenopausal bleeding
Lymph node metastases were found in 23% (n = 14) of the patients who underwent lymphadenectomy during their primary surgery
The multivariate analysis adjusted for classical clinicopathological factors showed that plasminogen activator inhibitor type-1 (PAI-1) and -2 and tissue plasminogen activator (tPA) were significantly independent prognostic factors for diseasefree survival (DFS) with a hazard ratios (HR) of 3.85, 3.90 and 2.53, respectively
Summary
Endometrial cancer (EC) causes early symptoms such as postmenopausal bleeding. The. To date, patients with EC are categorized into risk groups (low, intermediate, and high) based on known prognostic factors such as; depth of myometrial invasion (MI), differentiation grade, tumor histology and lymphovascular space invasion (LVSI). Journal of Cancer Research and Clinical Oncology (2020) 146:1725–1735 recurrence, whereas a part of the patients considered as high-risk will not (Salvesen et al 2012). In addition to histological prognostic factors several immunohistochemical and genetic markers have been described which could improve the categorization of these risk groups. The immunohistochemical loss of ER and PR expression is associated with lymph node metastases and disease recurrences (Trovik et al 1990). Expression of the L1 cell adhesion molecule (LCAM) seems to be one of the most powerful markers associated with a poor outcome in EC patients (Geels et al 2016; Bosse et al 2014)
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