Search

BACKGROUND Endometrial cancers (EC) are a heterogeneous group of malignant neoplasms differing in etiology, clinical-pathological features and prognosis. OBJECTIVES To determine the differences between the expression of selected molecular factors and find connections between them in order to isolate possible biomarkers influencing treatment options. MATERIAL AND METHODS The investigated data involved archival histological preparations obtained from uterine EC samples taken from 137 patients, treated surgically between 2007 and 2014. The immunohistochemical Dako EnVisionTM Flex+ method was applied. RESULTS The expression of ERβ, MLH1 and BRCA1 was lower in ECI than in ECII patients. The ERα expression was higher in early Federation internationale de gynecologie et d'obstetrique (FIGO) (IA) stages than in advanced (IB-IV) stages, while ERβ expression was significantly higher in advanced stages compared to stage IA and increased with grading. The BRCA1 expression also increased with grading. In both type I and type II EC patients, ERα expression correlated with MYH9 and BRCA1, while ERβ expression correlated with BAP expression. High expression of BRCA1 correlated with several proteins: BAP, MYH9 and FAK. High BAP expression also correlated with high MYH9 expression. A correlation in the expression of these proteins was also demonstrated in the group consisting only of patients with ECI. A significant correlation was found between BAP expression and MYH9 among patients diagnosed with ECI. In the ECII group, no correlation was found between the tested proteins. CONCLUSIONS The ECI and ECII patients differed in the studied molecular factors, mainly in terms of ER and BRCA1 expression. Changes in BRCA1 expression were linked to alterations in BAP expression, but were also associated with the proteins MYH9 and FAK.

The aim of the study was to assess the activity of fucoidan on the uterine sarcomas (MES-SA and ESS-1) and carcinosarcoma cell lines (SK-UT-1 and SK-UT-1B) and its toxicity on the human skin fibroblasts (HSF). Two uterine sarcomas and two carcinosarcoma cell lines were examined, as a control HSF were used. Cell viability was assessed with MTT test, apoptosis with caspase-3 activity and cell cycle by assessment of DNA synthesis. Fucoidan significantly decreases cell viability in SK-UT-1, SK-UT-1B, and ESS-1 cell lines, such effect was not observed in MES-SA. Fucoidan was not substantially affecting proliferation among normal cells. The tested agent induced apoptosis in all cell cultures used in the experiment. Fucoidan affects cell cycle of all tested cell lines except MES-SA by increasing percentage of cells in G0/sub-G1/G1 phase. Fucoidan do not only affect proliferation but induces apoptosis in selected uterine sarcoma and carcinosarcoma cell lines, so it has potential to be used as cytotoxic agent. Fucoidan seems to be promising anti-cancer agent for endometrial stromal sarcoma and carcinosarcoma. Electronic supplementary material The online version of this article (10.1007/s00005-019-00534-9) contains supplementary material, which is available to authorized users.

Background Previous studies have shown clinical relevance of programmed death-ligand 1 (PD-L1) and soluble PD-L1 (sPD-L1) in human cancers. However, still contradictory results exist. Our aim was evaluation of PD-L1-expressing monocytic myeloid-derived suppressor cells (M-MDSCs), monocytes/macrophages (MO/MA), tumour cells (TC) and immune/inflammatory cells (IC) as well as investigation of the sPD-L1 in ovarian cancer (OC) patients. Methods The group of 74 pretreatment women were enrollment to the study. The expression of PD-L1 on M-MDSCS and MO/MA was assessed by flow cytometry. The profile of sPD-L1 was examined with ELISA. The expression of PD-L1 in mononuclear cells (MCs) was analyzed using real time PCR. PD-L1 immunohistochemical analysis was prepared on TC and IC. An in silico validation of prognostic significance of PD-L1 mRNA expression was performed based microarray datasets. Results OC patients had significantly higher frequency of MO/MA versus M-MDSC in the blood, ascites and tumour (each p 0.05). Significantly higher accumulation of blood-circulating M-MDSC, MO/MA, PD-L1+M-MDSC, PD-L1+MO/MA and sPD-L1 was observed in patients versus control (p 0.05). The expression of PD-L1 was significantly higher on IC versus TC (p 0.05) except higher level of PD-L1+TC in the endometrioid versus mucinous tumours. Interestingly, blood-circulating sPD-L1 positively correlated with PD-L1+M-MDSCs (p = 0.03) and PD-L1+MO/MA (p = 0.02) in the blood but not with these cells in the ascites and tumours nor with PD-L1+TC/IC (each p > 0.05). PD-L1 and sPD-L1 were not predictors of overall survival (OS; each p > 0.05). Further validation revealed no association between PD-L1 mRNA expression and OS in large independent OC patient cohort (n = 655, p > 0.05). Conclusions Although PD-L1 may not be a prognostic factor for OC, our study demonstrated impaired immunity manifested by up-regulation of PD-L1/sPD-L1. Furthermore, there was a positive association between PD-L1+ myeloid cells and sPD-L1 in the blood, suggesting that sPD-L1 may be a noninvasive surrogate marker for PD-L1+myeloid cells immunomonitoring in OC. Overall, these data should be under consideration during future clinical studies/trials.

Introduction: mTOR inhibitors are anticancer agents affecting mTOR/AKT/PI3K pathway that is one of the most important in human cancer cells. Hyperactivation of mTOR/AKT/PI3K and overexpression of this pathway members are frequently reported in uterine sarcoma and carcinosarcoma. Present study is aimed to assess the activity of the two mTOR inhibitors (rapamycin - RAP and sapanisertib - MLN) as a single agent and combined with gemcitabine (GEM, one of substances commonly used in systemic anticancer treatment) in uterine sarcoma and carcinosarcoma in vitro models. Material and methods: SK-UT-1 and SK-UT1-B (uterine carcinosarcoma), MES-SA (leiomyosarcoma) and ESS-1 (endometrial stromal sarcoma) cell lines were used. An MTT assay was performed to examine the cytotoxicity of RAP, MLN and mixtures: RAP+MLN, RAP+GEM, MLN+GEM against these cells. The interactions between tested compounds were assessed in isobolographic analysis. Results and conclusions: Carcinosarcoma cell lines (both SK-UT-1 and SK-UT-1B) do not respond to RAP and respond relatively weakly to MLN treatment. Additive and supraadditive effects were noted for combined treatment with GEM and MLN. Endometrial stromal sarcoma cell line (ESS-1) occured to be sensitive to both RAP and MLN, but the response was stronger for MLN. Additive effect of all tested drug combinations was observed for ESS-1. Leiomyosarcoma cell line (MES-SA) was found sensitive to both mTOR inhibitors. Additive effects in combinations of GEM, RAP and MLN were observed, what makes them promising for future preclinical and clinical trials. Additivity with slight tendency towards antagonism between GEM and MLN observed in MES-SA cell line is unexpected finding and might prompt the mechanistic research aimed to explain this phenomenon.

Vitamin D

Additional file 4: Fig. S4. Kaplan–Meier graphs with overall survival of ovarian cancer patients a-h. Microarray datasets (online KM plotter database, JetSet best probe set) were used to validate the results of CD274 (PD-L1) mRNA expression including a. large independent cohort (n = 655) available from all datasets together and from each datasets separately including b. GSE18520 (n = 53), c. GSE19829 (n = 28), d. GSE26193 (n = 107), e. GSE27651 (n = 39), f. GSE30161 (n = 50), g. GSE63885 (n = 25) and h. GSE9891 (n = 285).

Additional file 3: Fig. S3. Kaplan–Meier graphs with overall survival of ovarian cancer patients a-j. PD-L1 protein expression on immune cells and tumour cells and sPD-L1 concentrations including a. PD-L1+M-MDSC in the peripheral blood (n = 43), b. PD-L1+MO/MA in the peripheral blood (n = 43), c. PD-L1+M-MDSC in the peritoneal fluid (n = 26), d. PD-L1+MO/MA in the peritoneal fluid (n = 26), e. PD-L1+M-MDSC in the tumour tissue (n = 29), f. PD-L1+MO/MA in the tumour tissue (n = 29), g. sPD-L1 in the plasma (n = 39), h. sPD-L1 in the peritoneal fluid (n = 22), i. PD-L1+TC (n = 29) and j. PD-L1+IC (n = 29); IC-inflammatory/immune cells, M-MDSC - myeloid-derived suppressor cells, MO/MA- monocytes/macrophages, PB-peripheral blood, PD-L1-programmed death-ligand 1, PF-peritoneal fluid, TC-tumour cells, TT-tumour tissue.

Additional file 2: Fig. S2. Comparative analysis of myeloid cell populations, programmed death-ligand 1 (PD-L1)-expressing myeloid cells and PD-L1 gene expression in the three tumour microenvironments (TMEs) of ovarian cancer (OC) patients. a. Analysis of the percentage of monocytic myeloid-derived suppressor cells (M-MDSCs) and monocytes/macrophages (MO/MA). b. Analysis of the expression profile of PD-L1 on M-MDSCs and MO/MA. c. Expression of PD-L1 in the mononuclear cells (MCs). For all analysis paired samples of blood, ascites and tumour tissue from OC patients were used (n = 10). For PD-L1 gene expression analysis RNA was extracted from the MCs isolated from the blood, ascites and tumour tissue. mRNA expression gene level of PD-L1 was determined using quantitative polymerase chain reaction (qPCR). Data were normalized to the glyceraldehyde 3-phosphate dehydrogenase (GAPDH; fold change). Horizontal lines within the boxes indicate the median and the whiskers indicate the minimum and maximum values.

Additional file 1: Fig. S1. Analysis of monocytic myeloid-derived suppressor cells (M-MDSCs) and monocytes/macrophages (MO/MA) as well as programmed death-ligand 1 (PD-L1)-expressing M-MDSCs and MO/MA in ovarian cancer (OC). Mononuclear cells (MCs) from the blood (n = 43), ascites (n = 26) and tumour tissue (n = 29) of OC patients were analyzed. MCs from the blood of healthy women (n = 15) were also examined. Analysis was performed using flow cytometry. MCs were stained for PD-L1+M-MDSCs and MO/MA using fluorochrome-labeled monoclonal antibodies (mAb) against HLA-DR, CD14 and PD-L1(CD274). Representative dot plots from the blood sample of OC patient of HLA-DR−/lowCD14+ M-MDSCs, HLA-DR+CD14+ MO/MA, PD-L1-expressing M-MDSC and PD-L1-expressing MO/MA are shown.

One of the many factors involved in the development of uterine fibroids is vitamin D deficiency. One aspect of this deficiency is decreased serum concentration of calcidiol-25(OH)D, a metabolite of D3 vitamin. The active form of vitamin D3, which arises after numerous enzymatic reactions, is calcitriol-1,25(OH)2D3; this compound is transported to various body tissues. Vitamin D possesses extra-genomic effects due to its influence on various signaling pathways, i.e., through activating tyrosine kinases and by genomic effects via binding to a specific nuclear receptor, vitamin D receptor (VDR). The vitamin D/VDR complex regulates the expression of genes and is involved in the pathogenesis of fibroids. Numerous studies have shown that vitamin D supplementation reduces fibroid size. It has also been shown that the expression of VDR in myoma tissue is significantly lower than in the uterine muscle tissue at the tumor periphery. However, the expression of VDR in non-myoma uterine muscle has not previously been investigated. Our VDR expression studies were performed immunohistochemically with tissue microarrays (TMA) in three tissue groups: 98 uterine myoma tissues, 98 uterine tissues (tumor margin), and 12 tissues of normal uterine muscle (i.e., without fibroids). A statistical analysis showed significantly lower VDR expression in uterine muscle at the periphery of the fibroid than in healthy uterine muscle. Lower expression of VDR at the periphery of the myoma compared to that in normal uterine muscle may indicate potential for new myomas. This observation and the described reduction in the size of fibroids after vitamin D supplementation supports the hypothesis of causal development of uterine fibroids and may be useful for the prevention of re-development in the event of their excision from the uterus.

Introduction Data on the possible role of peritoneal fluid free radical-mediated oxidative damage in the pathogenesis of endometriosis still remains inconsistent. The aim of the study was to determine iron metabolism markers and their influence on oxidative stress arameters in the peritoneal fluid of women with endometriosis. Material and methods 110 women with endometriosis and 119 patients with benign ovarian cysts were included in the study. All visible peritoneal fluid was aspirated during laparoscopy from the anterior and posterior cul-de-sacs. under direct vision to avoid blood contamination. Haemoglobin, iron, total oxidative status, and total antioxidant status were measured using standard colourimetric kits. Results Haemoglobin, iron levels, as well as total oxidative status values were significantly higher, whereas total antioxidant status values were significantly lower in the peritoneal fluid of patients with endometriosis, in comparison to the reference groups. No differences were observed in peritoneal fluid concentrations of all parameters measured in relation to the phase of the menstrual cycle. Conclusions Peritoneal fluid of women with endometriosis is characterized by disrupted iron metabolism. This is most likely related to an increased number of erythrocytes in the peritoneal cavity of endometriotic women, which leads to a higher concentration of haemoglobin in this environment. Impaired iron homeostasis may have a significant influence on the pathophysiology of peritoneal endometriosis by the direct impact of haemoglobin derivatives and/or formation of the pro-inflammatory and pro-oxidative environment. Peritoneal cavity oxidative stress occurs predominantly in women in advanced stages of the disease.

PURPOSE The aim of this study was to evaluate the influence of ovarian cancer cell lysates isolated from type I or type II ovarian cancer (OC) on the phenotype of monocyte-derived dendritic cells (Mo-DCs) and the cytokine profile. We also determined whether the Mo-DCs and tumor microenvironment, reflected by peritoneal fluid (PF) from type I or II ovarian cancer, could promote regulatory T cell (Tregs) differentiation from naive CD4+ lymphocytes in vitro. RESULTS Our results show a significant role of the ovarian cancer microenvironment reflected by PF from type I or II OC in the inhibition of the DC differentiation process. Interestingly, the percentage of cells co-expressing CD45 and CD14 antigens in the cultures stimulated with PF from both type I and type II OC was higher than in the control. Furthermore, the percentage of cells expressing CD1a, i.e., a marker of immature DCs, was significantly reduced in the cultures stimulated with PF from type I and type II OC. The results obtained show that ovarian cancer type II lysates induce differentiation of monocytes into macrophage-like cells with a CD1a+/HLA-DR+/CD83− phenotype and significantly higher CD86/HLA-DR expression. We show that ovarian cancer type II Mo-DCs are able to prevent an immune response by release of IL-10, whereas OC type I Mo-DCs can promote the generation of Tregs. CONCLUSIONS We demonstrate that each type of ovarian cancer can induce a unique phenotype of DCs and differentiation of Tregs, both associated with immune-suppressive function, which may be an obstacle while developing effective anticancer dendritic cell vaccination.

The objective of the study was to assess the level of patients' need for information about the planned gynecologic surgery. Material and Methods. The number of 173 patients preparing to undergo planned gynecological procedure were qualified for the study. The participation in the survey was entirely voluntary. Each patient was asked to fulfill the survey conducted using the Amsterdam Preoperative Anxiety and Information Scale- APAIS that enables the estimation of the patient’s need for surgery-related information. Furthermore patients’ clinical and demographic data was collected. Results were analyzed using appropriate statistical tools: the Shapiro-Wilk W-test (for distribution of the studied parameters) and the Mann-Whitney U-test (for comparing two independent groups). P value less than 0.05 was considered statistically significant. Results. It was shown that premenopausal women have a greater need for information about the planned surgery than postmenopausal patients (p0.05). Conclusions. The high level of the need for information about the planned surgery characterizes premenopausal patients and those operated for the first time.

Introduction/Background The results of systemic therapy among the most of patients suffering from uterine sarcomas and carcinosarcomas remains unsatisfactory. Strong need of further research on multi-drug regimens is widely postulated. To investigate this problem the collaboration in ENITEC group was raised. Methodology Two uterine sarcomas (MES-SA, ESS-1), two carcinosarcoma (SK-UT-1, SKUT-1B) cell lines and control line HSF (Human Skin Fibroblasts) were cultured. Cells were incubated in presence of gemcitabine, mTOR inhibitors (rapamycin, MLN0128) and natural compound (fucoidan). Cell viability was assessed with MTT test. The combinations of investigated drugs activities were assessed using isobolography. Additionally, apoptosis and cell cycle were assessed. Results Gemcitabine decreases cell viability among all tested cell lines with strongest effect in SK-UT-1, SK-UT-1B, and ESS-1. Rapamycin affects cell viability in ESS-1 and MES-SA but not carcinosarcoma and HSF cell lines. MLN0128 influenced cell viability among all tested lines but in ESS-1 and MES-SA in significantly lower concentration comparing to the others. Fucoidan significantly decreases cell viability in SK-UT-1, SK-UT-1B, and ESS-1 cell lines, but not in MES-SA. Fucoidan was not substantially affecting proliferation among normal cells. The isobolographic analysis revealed synergistic effect of following combinations: gemcitabine+fucoidan and gemcitabine+MLN0128 in SK-UT-1B. Antagonism of gemcitabine+MLN0128 was noticed in MES-SA cell line. The effects of other combinations of tested drugs were additive. Conclusion Fucoidan showed high activity against carcinosarcoma cell lines– due to its similarity to endometrial cancer further experiments with this substance are justified. MES–SA and ESS–1 lines are significantly more sensitive to mTORi comparing to others cell lines. Antagonistic effect between gemcitabine and MLN0128 in MES–SA might be avoided in designing future clinical trials– it’s mechanism should be clarified. Synergism observed between gemcitabine and novel agents (fucoidan and MLN0128) in carcinosarcoma cell line might be used in planning future therapies. Disclosure Nothing to disclose.

Introduction/Background Teratomas are type of germinal neoplasms derived from multipotential cells, may contain one to all tree germ layers. Usually localised in ovaries and testis due to migration of primary embrionic germ cells in developing embryo, mature teratomas found in other abdominal/pelvic locations are an extremely rare case. Methodology A 36-year-old patient reported to the doctor for routine gynecological examination. In transvaginal ultrasound a ‘small cystic-solid change in the right ovary’ was detected. The Ca-125 level was 29.1 U/ml. The patient was sent for a consultative examination to the ultrasound specialist. He found unchanged left ovary, and under it irregular form with mixed echogenicity. In the right adnexa was cystic-solid lesion with a highly vascularized solid field. The patient was referred for minimally invasive surgery. Next obtained results of laboratory tests: Ca-125 20,03U/ml and HE4 50 pmol/l. There were found unchanged uterus and ovaries, intraoperatively but both fallopian tubes were pathologically chanaged. The right fallopian tube was sent for an intraoperative study, giving a result suggesting teratocarcinoma of the fallopian tube. Results The histology revealed bilateral teratocarcinomas. Currently, patient stays under clinical surveillance. Conclusion In conclusion, teratomas of fallopian tubes are rarely encountred findings still should be considered in the differential diagnosis of extragonadal abdominal masses. Disclosure Nothing to disclose.

Purpose Cerebral metastases develop in 10–30% of patients with breast cancer (BC) and in around 3.3 to 4% of patients with ovarian cancer (OC). The aim of the multicenter study is to investigate the correlation between the expression of estrogen alpha receptors (ERα), progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), stromal cell-derived factor 1 (SDF1) and its receptor C-X-C chemokine receptor type 4 (CXCR4), breast cancer metastasis suppressor 1 (BRMS1), astrocyte elevated gene 1 (AEG1), depending on the status of BRCA1 protein, in patients suffering from OC and BC with brain metastases. Patients and methods The analysis included 51 patients: 29 with BC and 22 with OC, in whom brain metastases were disclosed. Results In most patients (65.5% of BC patients and 68.2% of patients with OC tumors) BRCA1 protein loss was found. No correlation was disclosed between the levels of ERα, PR receptors, HER2, SDF1, CXCR4, AEG1, BRMS1 and BRCA1 status, patient age, stage of disease advancement, grade of histological maturity of the cells, presence of metastases to lymph nodes. A statistically significant correlation was disclosed between the negative expression of PR receptors and a high expression of CXCR4 in patients with BC. High values of the AEG1 protein (linked to metastases) were detected alongside a high expression of BRMS1 (a suppressor of metastases). Conclusions Patients with BC and OC and brain metastases have a frequent loss of BRCA1 expression. The role of ERα, PR, HER2, SDF1, CXCR4, AEG1, BRMS1 in metastatic process needs further studies.

Objectives: The objective of the study was to retrospectively evaluate the density of vessels exhibiting positive glycoprotein CD34 expression in the uterine leiomyosarcoma tissues and their correlation with the age of patients at the time of tumor diagnosis. Material and methods: The archival paraffin blocks with the cancer tissues collected from 50 patients suffering from uterine leiomyosarcoma were used together with their clinical and demographic data. The immunohistochemical peroxidase-de­pendent methods were used to detect microvessels with positive CD34 expression. The glycoprotein CD34 expression was evaluated as a density of microvessel showing the positive immunohistochemical reaction (MVD CD34 ). Results: The negative, statistically significant correlation between the age of patients (at the moment diagnosis) and the MVDCD34+ (R = –0.289, p = 0.042) was found. Conclusions: The study’s findings may suggest that the tissues of younger people constitute a permissive environment for pro-angiogenic factors.

Vitamin D3 is a fat-soluble essential nutrient that affects multiple biologic functions in the organism through calcitriol and the vitamin D3 receptor. This review article focuses on the results of studies on the relationship between the level of vitamin D3 and cancer incidence or mortality, but also on the anticancer properties of vitamin D3 that support its significant role in the prevention, clinical course, and overall survival rates of selected cancers (colorectal, prostate, breast, ovarian, endometrial, bladder, and malignant melanoma). The mechanisms of vitamin D3 action involve, among others, polymorphism of vitamin D3 receptor, cell cycle, caspases, and cancer stem cells. The level of vitamin D3 has been also demonstrated to serve as a biomarker in some cancers, and high levels of vitamin D3 can be conducive to successful cancer therapy.

BACKGROUND Endometrial carcinomas (EC) differ in etiology, clinical course and prognosis. OBJECTIVES This multi-center study aimed at a closer recognition of molecular factors linked to heterogeneity of EC by evaluating estrogen and progesterone receptors, proteins dependent on MMR genes, proteins linked to poor prognosis and metastases, and mutations in BRCA1. MATERIAL AND METHODS Using sections of paraffin-embedded preparations, in 115 patients with EC type I and 31 with EC type II, expression of ERα, ERβ1, PR, MLH1, and MSH2 proteins, as well as ARID1A, c-MET and BRCA1, was estimated by immunohistochemistry using specific antibodies. RESULTS Expression of ERβ1 was augmented in EC type II, in poorly differentiated cancers and with growing clinical advancement. An augmented expression of ERα was noted in well-differentiated EC and at lower clinical stage. An increased expression of PR and decreased of MLH1 were detected in type I EC. The expression of ARID1A and c-MET proteins showed no differences between the types of EC, stages of clinical advancement or grading. In 51.6% patients with type II EC, a loss of BRCA1 expression was disclosed; in this group of cancers a decreased expression of ERα was noted. CONCLUSIONS An augmented expression of ERβ1 was linked to type II EC. A higher expression of ERα in EC cancers was associated with a lower histopathological grade. A decreased expression of MLH1 protein was estimated in EC type I. Type II EC may be connected to BRCA1 mutation.

Ovarian cancer is a serious diagnostic and clinical issue. It belongs to the group of cancers with the highest mortality rate, that is why new, effective methods of therapy have been sought after. In recent years, researchers have been paying attention to the use of immunothetapy in the treatment of ovarian cancer. Currently, the numer of studies with the use of PD-1/PD-L1 pathway inhibitors is increasing. It has been reported that PD-1 receptor and its ligand are expressed on tumor cells and immunology system cells in patients with ovarian cancer. Increased expression of PD-1/PD-L1 is one of the inhibition mechanisms of the anti-tumor response by induction of peripheral tolerance. That seems why blocking PD-1/PD-L1 may be so important. A significant role in activation of programmed death cell-1 is attributed to tumor microenvironment (TME). In this review we have described the meaning of PD-1/PD-L1 pathway in ovarian cancer pathogenesis and current results of clinical trials using PD-1/PD-L1 inhibitors. Numerous clinical trials are focused on the effectiveness of immunotherapies as both monotherapy and combination therapy. The promising results of initial research phases are the basis for taking action on a larger scale. Perhaps this will allow in the future to use inhibitors of the PD-1/PD-L1 pathway in the treatment of ovarian cancer.

Introduction and objective. The objective of the study was to present preliminary results of a pilot study concerning the level of knowledge of gynaecological prevention, conducted in teenagers referred by court rulings to a juvenile attendance centre. Materials and method. The instrument was an anonymous survey questionnaire completed by participants in health prevention classes in late 2010 and early 2011. The studied group consisted of teenagers aged 15–17 years (mean age: 15.72 years, median = 16 years, SD = 0.679) who were under probation officers’ supervision in the Zamość region of south-eastern Poland. The sample size was 101 persons – 51 boys (50.50%), 50 girls (49.5%). Results. According to the respondents, the most important reasons for seeing a gynaecologist were: menstrual disorders (70.30%), suspicion of pregnancy (63.37%) and pain or burning sensations while urinating (58.42%). The following were regarded as prevalent cancers in women: cancers of the breast (99.01%), cervix (89.1%), and ovaries (62.38%). Over 92% of subjects stated that it was possible to protect oneself from cervical cancer, but only 41.5% of respondents indicated the correct definition of the term ‘cytology’. Statistical analysis focused on differences between genders. A higher self-assessment of mental health was shown in boys. Conclusions. Teenagers of similar background may find it more difficult to gain access to knowledge about health prophylaxis, including gynaecological prevention. Efforts should be intensified in order to ‘equalize health opportunities’ through appropriate preparation of teaching curricula (including health education and philosophy of medicine).

I Chair and Department of Gynecological Oncology and Gynecology is a specialist research center providing help in diagnostics and treatment of gynecological malignancies. The research work is focused on the processes of angiogenesis and lymphangiogenesis. Development of blood and lymphatic vessels is subject to research in a wide range of malignancies, including ovarian cancer, endometrial cancer and uterine sarcomas. Angiogenesis in malignancies of the female genital tract is investigated by using some modern 3D sonography that uses high-definition blood flow imaging. Ovarian Tumors and Early Ovarian Cancer Detection unit was established in 2002 and since that time more than 3500 patients with difficult to diagnose tumors have been consulted and treated in the Department. Ovarian cancer immunology studies are the second leading research fiekld in the 1st Chair Department of Gynecological Oncology and Gynecology. The Department is well equipped with diagnostic devices as well as a scientific laboratory. This allows for studies in the fields of imaging of masses, their immunology, biochemistry and molecular biology. Understanding immunological response in patients with ovarian cancer is the key to develop new, effective therapies, including immunological vaccines. In this area we are cooperating with prominent international research centers: Department of Surgery, University of Michigan and Department of Microbiology and Immunology, University of Arkansas. Results of our research are published in both Polish and international journals specializing in fields of gynecology, oncology, immunology and basic science.

Uterine leiomyosarcomas (LMS) are rare tumors typically presenting rapid growth and unfavorable outcome. Nowadays the results of uterine LMS treatment do not meet expectations. Angiogenesis is one of processes investigated to be target for future treatment. The aim of the research was to assess microvessels density (MVD) in tumor samples collected from 50 patients with histological confirmed uterine leiomyosarcoma and to investigate statistical relations between MVD, patients survival, and FIGO stage of tumor. The assessment was carried out using immunohistochemistry methods with anti-CD34 antibody. No significant difference in MVD between FIGO stages was observed. Furthermore, contrary to many other malignancies, we found no significant relation between MVD and patients overall and 2-year survival. Results obtained in the study suggest that processes on vascular mimicry and mesenchymal to epithelial transition (MET) may play important role in development of LMS. No statistical relation between MVD and survival leads to conclusion that not only angiogenesis but other mechanisms as well should be taken into consideration in planning future research.

Objectives: The role of angiogenesis in leiomyosarcomas still remains unclear. The aim of this study was to evaluate the NRP1 expression in the leiomyosarcoma tissues and to find the relations between its expression and the clinical features. Material and methods: The study group consisted of 50 patients with diagnosis of the uterine leiomyosarcoma. Clinical and follow up data were collected. Using immunohistochemical methods the expression of NRP1 was detected. Results: The lack of NRP1 expression was found in 14 cases, positive (weak or moderate) expression was noted in 36 cases. The significantly higher expression of NRP1 was observed in more severe clinical stages in comparison to lower stages of the disease. The significantly shorter survival of patients with the positive expression of NRP1 in leiomyosarcoma was observed. Conclusions: The expression of NRP1 is associated with clinical advancement and worse prognosis in uterine LMS. Neuropilin 1 can be widely used as a postoperative survival predictor for the patients suffering from uterine LMS.

Ovarian cancer is a malignancy of high mortality rates. In respect of the number of deaths caused by cancers it occupies the fourth place among women in Poland. Recent studies are focusing on the role of immune system in ovarian cancer pathogenesis. It has been reported that immune response against ovarian cancer cells may be inhibited by a number of immunosuppressive mechanisms active in cancer microenvironment. It causes difficulties in recognizing and destroying cancer cells by immune system which leads to the development of immune tolerance and is associated with a low efficacy of standard therapeutic strategies. In the presented paper we have described selected, new immunosuppressive mechanisms in ovarian cancer patients. They may be a novel, additional and relevant criterion that should be considered whilst developing new therapeutic strategies. Possibly, modulation of immunosuppressive mechanisms could contribute to modifying standard therapies and in consequence improve treatment outcome in ovarian cancer patients.

The low incidence of uterine sarcomas requires many issues associated with its biology and clinical course to be followed with more research. Unsatisfactory surgical outcomes and a high risk of cancer dissemination make it worthwhile to consider the feasibility of supplementary systemic treatment. The currently employed chemo- and hormonal therapy is characterised by low efficacy. There is some hope in reports on targeted treatment. However, a comprehensive assessment of the efficacy of this kind of therapy is restricted by a small number of patients using it. Moreover, clinical studies using targeted therapies involve patients with a highly advanced disease, and the therapeutic results are assessed mainly via analysis of progression-free survival but not the clinical response.

Presence of fibrothecoma is not usually accompanied by elevated levels of tumor markers. In recent years, however, there have been isolated reports of fibrothecoma and Meigs’ syndrome, accompanied by an increase in tumor markers. We present a case of fibrothecoma with Meigs’ syndrome and elevated levels of both CA-125 (cancer antigen 125) and HE-4 (human epididymis protein 4). In this paper, we present a case of Meigs’ syndrome associated with an increased CA-125 and HE-4 level due to ovarian fibrothecoma.

Objective To evaluate 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-isoprostane levels in the peritoneal fluid (PF) of women with endometriosis. Study design One hundred and ten women with laparoscopically and histopathologically confirmed endometriosis and, as reference groups, 119 patients with simple serous (n = 78) and dermoid (n = 41) ovarian cysts were studied. Peritoneal fluid 8-OHdG and 8-isoprostane concentrations were evaluated by enzyme-linked immunosorbent assays. Results 8-OHdG and 8-isoprostane levels in peritoneal fluid were significantly higher in patients with endometriosis compared with the reference groups. Higher PF 8-OHdG and 8-isoprostane concentrations were observed in patients with advanced stages of endometriosis. A statistically significant positive correlation was found between 8-OHdG and 8-isoprostane levels in peritoneal fluid. Conclusion Endometriosis induces greater oxidative stress and frequent DNA mutations in peritoneal fluid than nonendometriotic ovarian cysts. The most severe oxidative stress occurs in the peritoneal cavity of women with more advanced stages of the disease.

Problem The initiation of labor is accompanied by alterations in the level of maternal immune tolerance toward fetal antigens. It is a complex molecular response leading to a brief activation of the maternal immune system with an accompanying capacity to restrict this same activation. The aim of our study was to evaluate the subpopulation of regulatory T cells (Tregs) and B7-H4 macrophages in the decidua basalis during cesarean sections performed on patients in various stages of labor. Method of study The decidual tissue samples evaluated in our study were obtained from 23 pregnant women who underwent cesarean sections at term. Moreover, the patients were divided into three subgroups according to the progression of labor at the time of the cesarean. The presence of Treg cells and B7-H4 positive macrophages were analysed by fluorescence-activated cell sorter. Results The percentages of FOXP3+ cells in the subpopulation of CD25+ CD4+ T lymphocytes found in the deciduas of patients decreased with the successive stages of labor, while the percentages of B7-H4 positive cells in the macrophage subpopulation remained almost constant. Conclusion These changes in the Treg cell subpopulation in the decidua would seem to be related to a brief activation of the maternal immune system as labor begins and lack of analogical changes in the subpopulation of decidual suppressive B7-H4+ macrophages that enable the restriction of this same activation as labor progresses.

Problem Alterations in RCAS1 (a receptor-binding cancer antigen expressed on SiSo cells) expression in the placenta and decidua may be related to the regulation of the process of maternal immune tolerance against fetal antigens. Moreover, it has been demonstrated that the occurrence of the spontaneous beginning of stillbirth is related to a decrease in the placental expression of RCAS1. There are no data currently available on the immune processes in decidua during stillbirth. The aim of this study was to evaluate the RCAS1 immunoreactivity level in decidua and to identify the cytotoxic immune cells present during labor, induced after intrauterine fetal death either with a combination of oxytocin (OT) and prostaglandins or with OT alone; a further objective was to assess the potential impact of these molecular alterations on the effectiveness of stillbirth induction. Methods The immunoreactivity of RCAS1, CD3, CD56, CD69, and CD25 was assessed by immunohistochemistry in 31 decidual samples derived from patients in whom the stillbirth occurred before the onset of labor. Results The RCAS1 immunoreactivity level was higher in a statistically significant manner in decidual tissue samples derived from patients in whom OT alone proved insufficient to induce labor after the diagnosis of intrauterine fetal death but required additionally the use of prostaglandins when compared with samples from women in whom stillbirth was induced successfully with OT alone. However, we did not observe any differences either in CD56 and CD3 positive cell presence or in CD25 and CD69 antigen immunoreactivity in the respective decidua of these two groups of patients. Conclusion The level of RCAS1 in decidua seems to influence the effectiveness of stillbirth induction.

The majority of adult women with endometriosis report that their symptoms started in adolescence. Early diagnosis and optimal treatment prevent disease progression and mitigate long-term morbidities, such as infertility and chronic pelvic pain.

Cyclin A is a cell-cycle regulatory gene and its overexpression promotes tumor cell growth. Y-Box-binding protein 1 (YB1) is a transcription/translation factor involved in tumor growth, invasion, and drug resistance. We investigated whether an association exists between protein products of these genes in epithelial ovarian cancer (EOC) specimens and clinicopathological parameters, patient response and EOC sensitivity to platinum-based first-line chemotherapy.Cyclin A and YB1 expression were analyzed by immunohistochemistry in 54 human primary EOC tissues. Immunolabeling of both proteins was graded according to their staining intensity (scale 0-3) and the proportion of immunostained cancer cells (scale 0-4) to obtain a staining index (SI; value=0-12).Significantly higher cyclin A immunostaining (SI≥4) in EOC specimens was discovered in patients with advanced (International Federation of Gynaecology and Obstetrics (FIGO) III and IV, p=0.003), poorly differentiated (G3, p0.001) tumors, and tumors of those with residual disease1 cm (p=0.001). YB1 immunostaining was significantly higher in EOCs from patients with suboptimal debulking (p=0.025). Over-expression of cyclin A (SI≥9) in EOCs was significantly linked with poorer patient response (p=0.001) and higher resistance of tumors to platinum-based first-line chemotherapy (p=0.007), while immunolabeling of YB1 in EOCs was not significantly associated with either of these variables (p0.05). Cyclin A expression was significantly and positively correlated with that of YB1 (R=0.588, p0.001).Increased cyclin A expression in EOC is related to a more aggressive tumor behavior and predicts the response of patients to first-line platinum-based chemotherapy.

Objectives: Most investigators agree that endometriosis is associated with a state of subclinical, non-infectious peritoneal inflammation. The objective of the study was to assess concentrations of two markers of the acute inflammatory phase proteins, haptoglobin and ceruloplasmin, in peritoneal fluid of endometriotic women. Material and methods: 229 women who underwent diagnostic or therapeutic laparoscopy were included in the study. Minimal, mild, moderate and severe endometriosis according to ASRM was confirmed in 119 women (study groups), whereas 110 patients suffered from simple serous or dermoid ovarian cysts (reference groups). Haptoglobin and ceruloplasmin concentrations in the peritoneal fluid samples aspirated during laparoscopy were measured using commercially available radial immunodiffusion kits. Results: The concentration of haptoglobin in the peritoneal fluid of women with endometriosis was significantly higher as compared to patients with serous and dermoid ovarian cysts. Significantly higher haptoglobin level was observed in patients with severe and moderate endometriosis as compared to women from both reference groups. No significant difference in the peritoneal fluid ceruloplasmin levels was found between patients with endometriosis and women from reference groups. However, it was noted that ceruloplasmin levels are higher in the subgroup of patients with severe endometriosis as compared to both reference groups and women with mild disease. Conclusions: Our results support the hypothesis that endometriosis is associated with subclinical inflammation within the peritoneal cavity. It may be speculated that pro-inflammatory stimuli strong enough to cause an increase in acute inflammatory phase proteins peritoneal fluid concentrations are observed only in the advanced stages of the disease.

Niska zgłaszalność kobiet na bezpłatne badania cytologiczne oferowane w ramach „Populacyjnego Programu Profilaktyki i Wczesnego Wykrywania Raka Szyjki Macicy” (PPPWWRSM) stanowi zagadnienie wymagające pogłębionej analizy. Przedstawiony projekt jest jednym z pierwszych reprezentatywnych badań socjologicznych, dotyczących tej problematyki. Głównym celem projektu były opis oraz interpretacja postaw kobiet wobec profilaktycznych badań cytologicznych, a także diagnoza przyczyn unikania/odkładania w czasie takich badań. Z uwagi na złożoność przedmiotu badań, zastosowano dwa rodzaje analizy: jakościową i ilościową. Przeprowadzono 80 wywiadów swobodnych, z których wnioski wykorzystano na etapie przygotowania narzędzia do badań o charakterze ilościowym. Wywiady bezpośrednie (CAPI) zostały zrealizowane jesienią 2014 r. na ogólnopolskiej reprezentatywnej próbie 500 kobiet w wieku 25–59 lat (populacja objęta PPPWWRSM). Efektem badań jest wiedza dotycząca zachowań zdrowotnych Polek oraz ich społecznych uwarunkowań. Na szczególną uwagę zasługują odmienne wzorce postępowania, wynikające ze zróżnicowania społeczno-kulturowego (m.in. wiek, miejsce zamieszkania, wykształcenie), przejawiające się w korzystaniu z opieki ginekologicznej, wiedzy na temat profilaktyki i jej źródeł oraz motywacji do podejmowania aktywności prozdrowotnej. Low attendance of women to free cytology tests under the “Population Program of Prevention and Early Detection of Cervical Cancer” (PPPWWRSM) is an issue that requires an in-depth analysis. The presented project is one of the first representative sociological inquiries concerning this subject. The main goal of the project was to describe and interpret the attitude of women towards preventive smear tests and the diagnosis of the reasons for avoidance/postponement in time of such tests. Because of the complexity of the object of research two kinds of analysis were employed: qualitative and quantitative. 80 free interviews were conducted, the conclusions having been used at the stage of preparing the instrument for quantitative research. Personal interviews (CAPI) were conducted in the autumn of 2014 on the nationwide representative sample of 500 women aged 25–59 years (the population covered by the PPPWWRSM). The result of research is the knowledge about the health behaviors of Polish women and their social determinants. Especially worth noting are different behavior patterns resulting from social-cultural diversity (inter alia age, place of residence, education), which manifest themselves in the use of gynecological care, knowledge about prevention and its sources, and in motivation for undertaking pro-health activities. Projekt został sfinansowany ze środków Narodowego Centrum Nauki przyznanych na pod- stawie decyzji numer DEC-2011/03/B/HS6/04503.