Department Obstetrics and Gynecology, Radboud University Medical Centre, Geert Grooteplein 10, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
J Cancer Res Clin Oncol. 2020 Jul;146(7):1725-1735. doi: 10.1007/s00432-020-03225-7. Epub 2020 May 11.
The 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).
Preoperative 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).
Serum 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.
Serum 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.
纤溶酶原激活物系统（PAS）和血管内皮生长因子（VEGF）在致癌作用中非常重要，并且在癌症侵袭和介导癌转移中起着关键作用。本研究的目的是评估血清 VEGF 水平和 PAS 成分与子宫内膜癌（EC）患者的临床病理危险因素和结局的相关性。
收集 1999 年至 2009 年间接受 EC 治疗的 173 例患者的术前血样。通过酶联免疫吸附试验（ELISA）评估血清 VEGF、尿激酶型纤溶酶原激活物（uPA）、组织型纤溶酶原激活物（tPA）、纤溶酶原激活物抑制剂-1（PAI-1）和 -2（PAI-2）的浓度。
血清 VEGF 和 PAS 成分水平与疾病分期、肿瘤组织学、肿瘤分级、肌层浸润（MI）、淋巴血管空间浸润（LVSI）和淋巴结转移（LNM）显著相关。与无疾病复发的患者相比，经历复发的患者术前血清 PAI-1 和 -2 以及 tPA 水平更高（p<0.01）。PAI-1 和 -2 以及 tPA 是 DFS 的显著独立预后因素，HR 分别为 3.85（95%CI 1.84-8.07）、3.90（95%CI 1.75-8.66）和 2.53（95%CI 1.16-5.55）。PAI-1 和 tPA 是 OS 的独立预后因素，HR 分别为 2.09（95%CI 1.08-4.05）和 2.16（95%CI 1.06-4.44）。
在原发性诊断时，血清 VEGF 和 PAS 成分水平与众所周知的临床病理危险因素相关，如 FIGO 分期、肿瘤组织学、肿瘤分级、MI、LVSI 和 LNM。高浓度的 PAI-1 和-2 以及 tPA 是子宫内膜癌患者预后不良的独立因素。
