Evaluation of biologically active substances promoting the development of or protecting against endometrial cancer

Aneta Cymbaluk-Płoska,1 Anita Chudecka-Głaz,1 Anna Jagodzińska,1 Ewa Pius-Sadowska,2 Agnieszka Sompolska-Rzechuła,3 Bogusław Machaliński,2 Janusz Menkiszak1 1Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, Szczecin, Poland; 2General Pathology Department, Pomeranian Medical University, Szczecin, Poland; 3Department of Statistics, West Pomeranian University of Technology, Szczecin, Poland Introduction: Adipose tissue is considered an endocrine organ and produces a number of biologically active substances. Aims: To consider the role that four adipokines – leptin, omentin-1, vaspin, and galectin-3 – play in the diagnosis of endometrium cancer and to investigate the association between serum concentrations of adipose tissue metabolism products and the diagnostics and prognosis in endometrial cancer. Patients and methods: The study included 168 patients with body mass index (BMI) >20 kg/m2 admitted due to post-menopausal bleeding. Results: A receiver operating characteristic curves test was performed to determine the diagnostic values of the proteins tested. For leptin and galectin-3 the area under the curve (AUC) values were 0.79/0.68, while for vaspin and omentin-1 the AUC values were 0.82/0.86 for all study patients. The final model identified the following independent risk factors: glucose concentration, BMI, waist circumference, leptin, and vaspin concentrations. Diagnostic values of leptin and galectin-3 with regard to differentiation between high (Fédération Internationale de Gynécologie Obstétrique [FIGO] III and IV) and low (FIGO I and II) stages of clinical tumor advancement and prediction of tumor grading (G1 vs G3) based on the AUC curve were 0.82/0.70 and 0.80/0.74. The AUC values for vaspin and omentin-1 with respect to differentiation between histopathological advancement and grading were 0.86/0.81 and 0.83/0.77, respectively. Significantly lower values of mean omentin-1 and vaspin concentrations were also demonstrated in cases of lymphatic vessel invasion, lymph node metastases, or deep endometrial infiltration (p=0.002, p=0.01, p=0.003, respectively). Conclusion: It appears that elevated concentrations of leptin, vaspin, and omentin-1 may indicate the presence of endometrial cancer. Furthermore, leptin serum level and vaspin appear to be useful tools in the assessment of clinical staging of endometrial cancer. Keywords: endometrial cancer, adipokines, leptin, vaspin, galectin-3, omentin-

Assessment of selected cytokines, proteins, and growth factors in the peritoneal fluid of patients with ovarian cancer and benign gynecological conditions

Anita Monika Chudecka-Głaz,1 Aneta Alicja Cymbaluk-Płoska,1 Janusz Leszek Menkiszak,1 Ewa Pius-Sadowska,2 Bogusław Bronisław Machaliński,2 Agnieszka Sompolska-Rzechuła,3 Izabella Anna Rzepka-Górska1 1Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, Szczecin, Poland; 2Department of General Pathology, Pomeranian Medical University, Szczecin, Poland; 3Department of Mathematics Applications in Economy, West Pomeranian University of Technology, Szczecin, Poland Objectives: The ovarian tumor microenvironment, ie, the peritoneal fluid, is an intriguing research subject. The goal of this study was to assess the behavior of selected cytokines and growth factors within the peritoneal fluid in pathologies associated with ascites and to assess the relationship between the levels of these substances and select prognostic factors of ovarian cancer. Methods: A total of 74 patients were enrolled in the study, including 36 patients with ovarian cancer and 38 patients with benign gynecological conditions. Peritoneal fluid collected during surgical procedures was used to assess the levels of interleukin (IL)-6, IL-8, stem cell factor (SCF), dickkopf-1, growth differentiation factor-15 (GDF-15), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), osteoprotegerin (OPG), osteopontin, osteonectin, and human epididymis protein 4. The median levels of these factors were compared between the two groups, and the levels of selected factors were assessed in the ovarian cancer group with regard to the clinical stage of cancer, tumor differentiation, presence of peritoneal spread and positive peritoneal fluid cytology results. The diagnostic value of the analyzed proteins within the peritoneal fluid was also assessed. Results: Differences were observed between the patients with ovarian cancer and the patients with benign gynecological conditions associated with ascites with regard to the levels of IL-6, IL-8, GDF-15, SCF, osteopontin, osteonectin, and OPG. There were no differences in dickkopf-1, TRAIL, and human epididymis protein 4 levels between the two study groups. Cancer stage affected only the mean SCF and OPG levels, with lower SCF values and higher OPG values in advanced cancers compared to less-advanced cancers. Tumor differentiation was associated with significantly lower SCF values in the group of poorly differentiated tumors. A significant reduction in SCF values and a significant increase in OPG and IL-6 values were also observed within cancer cell-positive peritoneal fluid. Peritoneal spread was associated with higher levels of TRAIL, osteonectin, and IL-6 in ovarian cancer patients. Conclusion: On the basis of the conducted studies, it appears that of the studied factors, GDF-15, SCF, and OPG deserve special attention in the context of future research on the tumor microenvironment. With regard to diagnostics, attention should be given primarily to GDF-15, IL-6, and osteonectin. Keywords: ovarian cancer, ascites, cytokines, tumor growth factor, GDF-15, SC