Marek Grabiec

The frequency of CD25+CD4+ and FOXP3+ regulatory T cells in ectopic endometrium and ectopic decidua

BackgroundThe presence of regulatory T (Treg) cells in human endometrium is crucial for maintaining immunological homeostasis within the uterus. For this study we decided to evaluate the subpopulations of Treg cells in conditions where a disturbance in the immunological equilibrium in ectopic endometrium and decidua has been observed, such as in cases of ovarian endometriosis (involving local immune cell suppression) and ectopic pregnancy (involving an increase in local immune system activity). We then compared these findings to what we observed in the normal eutopic endometrium of women during the secretory phase of the menstrual cycle (with immune cells under individual control).MethodsThe endometrium tissue samples evaluated in our study were obtained from 47 women during one of two kinds of laparoscopic procedures. 16 of the women underwent laparoscopies due to Fallopian tube pregnancies (EP), and 16 due to ovarian endometrioma, while 15 women made up a control group. The presence of regulatory T cells in these tissue samples was evaluated by FACS.ResultsIn our study, the percentages of FOXP3+ cells within the subpopulation of CD4+ T lymphocytes found in the decidua of the patients treated for Fallopian tube pregnancies were statistically significantly lower than both those observed in the ovarian endometriosis tissue samples and those found in the secretory eutopic endometrium samples of the control group.ConclusionThe disturbance in the immunological equilibrium observed in ectopic endometrium and decidua would seem to be related to the alteration in the Treg cell population that occurs in these ectopic tissues.

25(OH)D3 in patients with ovarian cancer and its correlation with survival.

OBJECTIVES The aim of this study was to examine vitamin 25(OH)D3 concentration in ovarian cancer patients in relation to a pathological subtype of the tumor, FIGO stage, grading, menopause status and overall 5-year survival. DESIGN AND METHODS 72 epithelial ovarian cancer patients aged 37-79, who undergone optimal cytoreductive surgery were enrolled to the study group. Serum 25(OH)D3 concentration was measured using an electrochemiluminescence immunoassay before surgery. Serum concentration of 25(OH)D3 was also measured in a group of 65 healthy non-obese women aged 35-65 years. RESULTS In patients with ovarian cancer serum concentration of 25(OH)D3 was lower than in the reference group (12.5±7.75 ng/mL vs 22.4±6.5 ng/mL). No significant correlation was found between serum 25(OH)D3 concentration and histological subtype, grading, FIGO stage and menopausal status. The study group was divided into two subgroups and the survival curves were analyzed. Overall 5-year survival rate was significantly higher in the subgroup of patients with 25(OH)D3 concentration over 10 ng/mL compared to women with concentration below 10 ng/mL. CONCLUSIONS Low 25(OH) D3 concentration associated with lower overall survival rate might suggest for the important role of severe deficiency in more aggressive course of ovarian cancer. Testing for 25(OH)D in the standard procedure could help to find ovarian cancer patients with worse prognosis, who would benefit of special attention and supplementation.

The preoperative maximum standardized uptake value measured by 18F-FDG PET/CT as an independent prognostic factor of overall survival in endometrial cancer patients.

Purpose. The aim of this study was to determine if the preoperative maximum standardized uptake value (SUVmax) measured by 18F-FDG PET/CT in the primary tumor has prognostic value in the group of patients with endometrial cancer. Patients, Materials, and Methods. A total of one hundred one consecutive endometrial cancer patients, age range 40–82 years (mean 62 years) and FIGO I–IV stage, who underwent 18-FDG-PET/CT within two weeks prior radical surgery, were enrolled to the study. The maximum SUV was measured and compared with the clinicopathologic features of surgical specimens. The relationship between SUVmax and overall survival was analyzed. Results. The mean preoperative SUVmax was 14.34; range (3.90–33.80) and was significantly lower for FIGO I than for higher stages (P = 0.0012), as well as for grade 1 than for grade 2 and 3 (P = 0.018), deep myometrial invasion (P = 0.0016) and for high risk group (P = 0.0004). The analysis of survival ROC curve revealed SUVmax cut-off value of 17.7 to predict high risk of recurrence. Endometrial cancer patients with SUVmax higher than 17.7 characterized by lower overall survival. Conclusion. The preoperative SUVmax measured by 18F-FDG PET/CT is considered as an important indicator reflecting tumor aggressiveness which may predict poor prognosis. High value of SUVmax would be useful for making noninvasive diagnoses and deciding the appropriate therapeutic strategy for patients with endometrial cancer.

Expression of Estrogen Receptors (α, β), Cyclooxygenase-2 and Aromatase in normal endometrium and endometrioid cancer of uterus

PURPOSE Endometrial cancer (EC) is one of the most common malignancies of the female genital tract, but the etiology, especially its metabolism is still investigated. The aim of this study was to evaluate the presence and relative expression of Estrogen Receptors (α, β), Cyclooxygenase-2 and Aromatase in both endometrial cancer and normal mucosa. MATERIAL/METHODS Two groups of women were selected for the study: 1) patients with endometrioid endometrial cancer (FIGO I; G1 - G3) (n=35) and 2) subjects with normal endometrial tissue (control group, n=29). The expression of Estrogen Receptors (ERα, β), Cyclooxygenase-2 (COX-2), Aromatase were estimated by Western blot analysis. Furthermore, the associations between FIGO classification (stage: Ia, Ib), tumor grade (G) and expression of ERα, β, COX-2, aromatase proteins were evaluated. Overall and disease-free survival curves were generated according to the Kaplan-Meier method. Median follow-up time of the patients examined in this study was 39 months. RESULTS The relative expression of each examined protein was markedly higher in the endometrial cancer tissue as compared to the healthy endometrium. The trends towards greater expression along with a tumor progression was noticed (FIGO stage: Ia vs. Ib). Analysis of endometrial cancer risk factors and their influence on survival curves showed only an inverse significant correlations between obesity (BMI: 36.2; n=21) and disease-free survival in EC group (p=0.00872), but there was no significant association between obesity and overall survival (p=0.358). CONCLUSIONS Endometrioid endometrial cancer shows relatively higher expression of either ER, COX-2 and aromatase comparing to healthy mucosa, suggesting their involvement in tumor development and progression.

The Role of Hypoxia-Inducible Factor-1α, Glucose Transporter-1, (GLUT-1) and Carbon Anhydrase IX in Endometrial Cancer Patients

Hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (GLUT-1), and carbon anhydrase IX (CAIX) are important molecules that allow adaptation to hypoxic environments. The aim of our study was to investigate the correlation between HIF-1α, GLUT-1, and CAIX protein level with the clinicopathological features of endometrial cancer patients. Materials and Methods. 92 endometrial cancer patients, aged 37–84, were enrolled to our study. In all patients clinical stage, histologic grade, myometrial invasion, lymph node, and distant metastases were determined. Moreover, the survival time was assessed. Immunohistochemical analyses were performed on archive formalin fixed paraffin embedded tissue sections. Results. High significant differences (P = 0.0115) were reported between HIF-1α expression and the histologic subtype of cancer. Higher HIF-1α expression was associated with the higher risk of recurrence (P = 0.0434). The results of GLUT-1 and CAIX expression did not reveal any significant differences between the proteins expression in the primary tumor and the clinicopathological features. Conclusion. The important role of HIF-1α in the group of patients with the high risk of recurrence and the negative histologic subtype of the tumor suggest that the expression of this factor might be useful in the panel of accessory pathomorphological tests and could be helpful in establishing more accurate prognosis in endometrial cancer patients.

Elevation of sE-Selectin Levels 2–24 Months following Gestational Diabetes Is Associated with Early Cardiometabolic Risk in Nondiabetic Women

Objective. We hypothesised that the endothelial dysfunction is associated with early glucose dysregulation and/or atherosclerosis risk factors in nondiabetic women with a previous history of gestational diabetes (pGDM). Material/Methods. Anthropometric parameters, glucose regulation (OGTT), insulin resistance (HOMA), lipids, biomarkers of endothelial dysfunction, and inflammation were evaluated in 85 women with pGDM and in 40 controls 2–24 months postpartum. Results. The pGDM group consisted of 67% normoglycemic women (pGDM-N) and 33% with prediabetic state (pGDM-P). The BMI, waist circumference, fasting and 2 h glucose (OGTT), soluble adhesion molecules, tissue plasminogen activator antigen, high sensitivity C-reactive protein, total-, LDL-cholesterol, and triglycerides/HDL-cholesterol ratio were higher in the pGDM women compared with the controls. After adjustment for BMI and fasting glucose, only higher triglycerides, higher TG/HDL and lower HDL-cholesterol were associated with pGDM. The pGDM-P differed from pGDM-N for only higher triglycerides and TG/HDL. The plasma level of sE-selectin was not independently associated with glucose concentration in pGDM group. sE-selectin level correlated with triglycerides, TG/HDL, plasminogen activator inhibitor-1 antigen, and sICAM-1. Conclusions. sE-selectin level correlated with components of metabolic syndrome, but only the atherogenic lipid profile was independently associated with a previous history of GDM in nondiabetic women 2–24 months postpartum.

The expression of suppressor of cytokine signaling 1 and 3 in fat and placental tissue from women with gestational diabetes

The suppressor of cytokine signaling (SOCS) proteins are feedback inhibitors of signaling pathways induced by cytokines, hormones and growth factors. In the present study we measured the expression of SOCS1, SOCS3, interleukin-6 (IL-6), IL-6 receptor, IL-8 and leptin mRNA in paired samples of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placental tissue obtained from 18 pregnant women with normal glucose tolerance (NGT) and 20 subjects with gestational diabetes mellitus (GDM), using quantitative RT-PCR. The patients with GDM had significantly higher IL-8 mRNA expression in VAT than the women with NGT (p = 0.007), whereas the expression of SOCS1, SOCS3 and other genes study did not differ significantly between the two groups. Stepwise regression analysis revealed that SOCS1 mRNA expression in VAT was significantly associated with prepregnancy BMI (β = −0.68, p = 0.03) and IL-8 mRNA expression (β = 0.66, p = 0.03), whereas SOCS3 mRNA expression in VAT was independently predicted by IL-6 mRNA expression (β = 0.94, p = 0.0002, R2 = 0.88). In conclusion, our results did not show significant differences in SOCS1 and SOCS3 mRNA expression in adipose and placental tissue obtained from pregnant women with and without GDM.

Prenatally evolving ectopia cordis with successful surgical treatment.

Ectopia cordis (EC) is a rare malformation due to failure of maturation of the midline mesodermal components of the chest and abdomen. It can be defined as a complete or partial displacement of the heart outside the thoracic cavity. It comprises 0.1% of congenital heart diseases. Common cardiac anomalies associated with EC are ventricular septal defect, atrial septal defect, and tetralogy of Fallot. EC and additional anomalies usually lead to intrauterine death. The possibility and efficacy of surgery in a surviving neonate depends on the degree of EC, coexisting congenital heart defects and extracardiac malformations. We present a case of prenatally diagnosed isolated EC diagnosed in the first half of pregnancy. After counseling, the patient decided to continue her pregnancy which ended with a newborn baby discharged from the hospital after cardiac surgery performed just after elective cesarean section.

ORIGINAL ARTICLE: Differences in the Soluble HLA-G Blood Serum Concentration Levels in Patients with Ovarian Cancer and Ovarian and Deep Endometriosis

Citation Mach P, Blecharz P, Basta P, Marianowski P, Skret‐Magierlo J, Kojs Z, Grabiec M, Wicherek L. Differences in the soluble HLA‐G blood serum concentration levels in patients with ovarian cancer and ovarian and deep endometriosis. Am J Reprod Immunol 2010

RCAS1 Decidual Immunoreactivity in Severe Pre-Eclampsia: Immune Cell Presence and Activity

Pre‐eclampsia seems to be related to the disturbance of immune tolerance regulation during pregnancy. Receptor‐binding cancer antigen expressed on SiSo cells (RCAS1) decidual level alterations were concomitant with changes in immune cell number and activity in decidua. As decidual immunomodulating activity participates in the development of immune tolerance during pregnancy, we aimed to evaluate the immunoreactivity level of decidual RCAS1 with respect to the presence and activity of immune cells.