Decreased s-Tie2 plasma concentration in patients with endometrioid endometrial cancer

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Abstract

IntroductionEndometrial cancer (EC) is the most frequent gynecological malignancy in more developed countries. Although the majority of patients are diagnosed at an early stage and cured by hysterectomy, the cancer recurs in about 20% patients with no sign of advanced/metastatic disease with limited response to systemic therapy. Identification of novel biomarkers for EC would be invaluable for preoperative stratification of patients as low/high-risk, detection of primary and recurrent disease and thus enabling personalized therapeutic approaches. Angiogenesis, formation of new microvessels from existing capillaries, is a complex process that plays an important role in the development and progression of several types of cancer, including EC. The process of angiogenesis is controlled by angiogenic factors (AF) expressed on the surface of the endothelial cells. Currently, AF have been studied in some malignancies but their role in EC has not been determined yet. In our study, we analyzed plasma concentration of 20 different AF in patients with the endometrioid type of EC. MethodologyProspective case – control study of women who underwent surgical treatment at the University Medical Centre Ljubljana (38 patients with endometrioid EC and 38 control patients with prolapsed uterus or myoma). Plasma samples were measured using commercially available kit that enables simultaneous determination of 20 different AF with the Luminex xMAP multiplexing technology. Analysis of experimental data was carried out using 5–parameter weighted logistic regression modelling on the xPonent 4.2. Software and plasma samples were diluted 5-fold prior to analysis.ResultsThe case group comprised 38 patients with endometrioid EC, with mean age 65.9 ± 8.2 years and mean body mass index (BMI) of 31.8 ± 6.1 kg/m2. Lymphovascular invasion (LVI) was present in five patients while deep myometrial invasion (DMI) was present in 12 patients. The control goup included 38 patients with mean age 66.8 ± 8.3 years and mean BMI of 27.6 ± 3.9 kg/m2. There was a significant difference in the BMI distribution between the case and control group (p<0.01). All patients were postmenopausal. Plasma levels of sTie-2 (soluble angiopoietin-2) showed significantly decreased levels in patients with EC compared to the control group (p<0.05). Tenascin C and angiostatin showed decreased levels in patients with EC and present LVI or DMV, respectively, while osteopontin levels were increased in patients with EC and present DMI, but these differences did not reach statistical significance. Based on different grade of endometriod EC neuropilin showed significant difference between grade 1 and 3.ConclusionResults of our pilot study indicate that plasma levels of different angiogenic factors might have a diagnostic and/or prognostic value in endometrioid EC. Further statistical evaluation and modeling is currently ongoing.DisclosuresNothing to disclose.
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