Endogenous Digitalis-like Factors as a Key Molecule in the Pathophysiology of Pregnancy-Induced Hypertension and a Potential Therapeutic Target in Preeclampsia.

Preeclampsia (PE), the most severe presentation of hypertensive disorders of pregnancy, is the major cause of morbidity and mortality linked to pregnancy, affecting both mother and fetus. Despite advances in prophylaxis and managing PE, delivery of the fetus remains the only causative treatment available. Focus on complex pathophysiology brought the potential for new treatment options, and more conservative options allowing reduction of feto-maternal complications and sequelae are being investigated. Endogenous digitalis-like factors, which have been linked to the pathogenesis of preeclampsia since the mid-1980s, have been shown to play a role in the pathogenesis of various cardiovascular diseases, including congestive heart failure and chronic renal disease. Elevated levels of EDLF have been described in pregnancy complicated by hypertensive disorders and are currently being investigated as a therapeutic target in the context of a possible breakthrough in managing preeclampsia. This review summarizes mechanisms implicating EDLFs in the pathogenesis of preeclampsia and evidence for their potential role in treating this doubly life-threatening disease.

Association of Membranous WNT-1 and Nuclear mTOR with Endometrial Cancer Grade.

Endometrial cancer remains a common cancer affecting the female reproductive system. There is still a need for more efficient ways of determining the degree of malignancy and optimizing treatment. WNT and mTOR are components of signaling pathways within tumor cells, and dysfunction of either protein is associated with the pathogenesis of neoplasms. Therefore, the aim of our study was to assess the impact of subcellular WNT-1 and mTOR levels on the clinical course of endometrial cancer. WNT-1 and mTOR levels in the plasma membrane, nucleus, and cytoplasm were evaluated using immunohistochemical staining in a group of 64 patients with endometrial cancer of grades 1-3 and FIGO stages I-IV. We discovered that the levels of WNT-1 and mTOR expression in the cellular compartments were associated with tumor grade and staging. Membranous WNT-1 was negatively associated, whereas cytoplasmic WNT-1 and nuclear mTOR were positively associated with higher grading of endometrial cancer. Furthermore, nuclear mTOR was positively associated with FIGO stages IB-IV. To conclude, we found that the assessment of WNT-1 in the cell membrane may be useful for exclusion of grade 3 neoplasms, whereas cytoplasmic WNT-1 and nuclear mTOR may be used as indicators for confirmation of grade 3 neoplasms.

[The influence of age, place of living, education and number of earlier pregnancies on attendance of pregnant women to screening tests--questionnaire study]. / Wplyw wieku, miejsca zamieszkania, wyksztalcenia i Iiczby wczesniejszych ciaz na zglaszalnosc ciezarnych do badan przesiewowych- badanie ankietowe.

UNLABELLED: The aim of this study was to assess attendance at the screening programme in pregnancy and the influence of age, number of past pregnancies, level of education and place of residence on the attendance. MATERIAL AND METHODS: Our study was performed on the basis of an anonymous questionnaire handed out 543 women aged 16-45, on the third day of their puerperal, in one of the five obstetric wards in southern Poland. The questionnaire contained questions about participation in recommended for pregnant women screening tests such as: fasting blood glucose level measurement, oral glucose tolerance test, blood type test, measurement of hepatitis B surface antigen and antibodies to VDRL, Rubella, Toxoplasma gondii, hepatitis C virus at least once during pregnancy. RESULTS: The highest attendance rate was related with blood type test, whereas the lowest was related with measurement of antibodies to hepatitis C virus (95.6% vs 22.7%, p < 0.001). A very low percentage of pregnant patients measured Rubella antibodies (29.1%). A larger proportion of the respondents checked antibodies against Toxoplasma gondii (41.6%). The attendance at fasting blood glucose level was 66.9 % and at oral glucose tolerance test was 63.7%. The attendance according as age, place of living, number of past pregnancies and level of education was described in detail. CONCLUSION: Despite current recommendations of Polish Gynecological Society and the ordinance of polish Minister of Health the percentage of women participating in screening tests during pregnancy is still insufficient. Age, place of residence and education remain strong factors influencing attendance at the screening programme in pregnancy.

[Carbon monoxide poisoning in pregnant woman]. / Zatrucie tlenkiem wegla u kobiety ciezarnej.

Carbon monoxide poisoning is one of the most frequent types of poisoning caused by gases. Exposure of a pregnant woman to carbon monoxide is connected with transmission of this gas to her fetus what may cause oxygen deficiency, and further, the damage to its organs. The article describes a case of carbon monoxide poisoning of a 28-weeks pregnant woman who was treated in a hyperbaric chamber. Therapy was successful and the woman gave birth to a healthy, full term infant. In case of poisoning to a pregnant woman the above seems to be the most advantageous solution.

Low androgen/progesterone or high oestrogen/androgen receptors ratio in serous ovarian cancer predicts longer survival.

The treatment of ovarian cancer (OC) remains one of the greatest challenges in gynaecological oncology. The presence of classic steroid receptors in OC makes hormone therapy an attractive option; however, the response of OC to hormone therapy is modest. Here, we compared the expression patterns of progesterone (PGR), androgen (AR) and oestrogen alpha (ERα) receptors between serous OC cell lines and non-cancer ovarian cells. These data were analysed in relation to steroid receptor expression profiles from patient tumour samples and survival outcomes using a bioinformatics approach. The results showed that ERα, PGR and AR were co-expressed in OC cell lines, and patient samples from high-grade and low-grade OC co-expressed at least two steroid receptors. High AR expression was negatively correlated, whereas ERα and PGR expression was positively correlated with patient survival. AR showed the opposite expression pattern to that of ERα and PGR in type 1 (SKOV-3) and 2 (OVCAR-3) OC cell lines compared with non-cancer (HOSEpiC) ovarian cells, with AR downregulated in type 1 and upregulated in type 2 OC. A low AR/PGR ratio and a high ESR1/AR ratio were associated with favourable survival outcomes in OC compared with other receptor ratios. Although the results must be interpreted with caution because of the small number of primary tumour samples analysed, they nevertheless suggest that the evaluation of ERα, AR and PGR by immunohistochemistry should be performed in patient biological material to plan future clinical trials.

Risk of Cesarean Delivery after Vaginal Inserts with Prostaglandin Analogs and Single-Balloon Catheter Used for Cervical Ripening and Induction of Labor.

(1) Background: Induction of labor is currently the most frequently performed procedure in modern obstetrics, referring to more than one in five women, and it is postulated that the percentage of labor induction will increase. (2) Methods: In total, 2935 patients in uncomplicated full-term pregnancy fulfilled the study inclusion criteria and underwent induction of labor. Pregnant women were divided into three groups: IOL with Dinoprostone, Misoprostol vaginal suppositories, and Foley catheter. Outcomes, including cesarean section rates, time to delivery, and cesarean section indications, were analyzed. (3) Results: There was statistically significantly more cesarean sections within 24 h in the Misoprostol group in comparison with the Dinoprostone and Foley catheter groups (p < 0.0001). The percentage of patients who had a cesarean section due to clinically diagnosed threatened fetal asphyxia was 63% in the Dinoprostone group, 81.3% in the Misoprostol group, and 55.3% in the Foley catheter group. There were statistically significantly more cesarean deliveries due to nonreassuring fetal heart rate patterns within 24 h in the Misoprostol group in comparison with the Dinoprostone and Foley catheter groups (p = 0.0031 and p = 0.0363). (4) Conclusions: Misoprostol may cause a more turbulent and violent course of labor, with a higher rate of increased incidence of nonreassuring fetal heart rate patterns and cesarean deliveries. The use of a Dinoprostone vaginal insert or Foley catheter may provide longer labor, although still within 48 h, with a lower risk of cesarean section caused by nonreassuring fetal heart rate patterns.

Results of Induction of Labor with Prostaglandins E1 and E2 (The RIPE Study): A Real-World Data Analysis of Obstetrical Effectiveness and Clinical Outcomes of Pharmacological Induction of Labor with Vaginal Inserts.

Despite extensive knowledge of the mechanisms responsible for childbirth, the course of labor induction is often unpredictable. Therefore, labor induction protocols using prostaglandin analogs have been developed and tested to assess their effectiveness in labor induction unequivocally. A total of 402 women were collected into two groups-receiving vaginal Misoprostol or vaginal Dinoprostone for induction of labor (IOL). Then, the patients were compared in groups depending on the agent they received and their gestational age. Most patients delivered within 48 h, and most of these patients had vaginal parturition. Patients who received the Dinoprostone vaginal insert required statistically significantly more oxytocin administration than patients who received the Misoprostol vaginal insert. Patients who received the Misoprostol vaginal insert used anesthesia during labor statistically more often. Patients who received Misoprostol vaginal inserts had a statistically significantly shorter time to delivery than those with Dinoprostone vaginal inserts. The prevalence of hyperstimulation was similar in all groups and remained low. Vaginal Misoprostol-based IOL is characterized by a shortened time to delivery irrespective of the parturition type, and a lower need for oxytocin augmentation, but also by an increased demand for intrapartum analgesia administration. A vaginal Dinoprostone-based IOL protocol might be considered a more harmonious and desirable option in modern perinatal care.

The 300 versus 300 Study-Low Volume versus High Volume Single Balloon Catheter for Induction of Labor: A Retrospective Case-Control Study.

The use of a Foley catheter is one of the oldest known methods of labor induction. Therefore, protocols using different volumes of Foley catheter balloons have been developed and tested to accurately determine their effectiveness. In this study, it was decided to retrospectively evaluate two induction of labor (IOL) protocols. The last 300 eligible patients who met the criteria and underwent the low-volume balloon protocol (40-60 mL) IOL were selected. Then next, 300 patients who met the criteria and underwent high-volume balloon (80-100 mL) IOL were selected. Outcomes included time to delivery and parturition type, oxytocin augmentation, operative deliveries and application of intrapartum anesthesia. Overall, the majority of patients delivered within 24 h. Patients who received a high-volume Foley catheter had statistically significantly more vaginal deliveries. The mean-time to delivery in the high-volume catheter group was statistically significantly shorter than in the low-volume catheter group. Patients who received a high-volume Foley catheter required statistically significantly less oxytocin augmentation during induction of labor compared to patients with a low-volume Foley catheter. Regardless of the balloon volume used, the percentage of operative deliveries remained at a similar, low level (8.36% and 2.14%). Regardless of the catheter volume used, the majority of patients chose epidural over intravenous anesthesia. In conclusion, a high-volume balloon Foley catheter IOL is characterized by an increased percentage of vaginal deliveries, shortened time to delivery regardless of the type of delivery, and lower need for oxytocin augmentation.

Nonsteroidal anti-inflammatory drug with a local anesthetic compared to nonsteroidal anti-inflammatory drug alone significantly reduce the pain associated with vaginoscopic office hysteroscopy.

INTRODUCTION AND OBJECTIVES: Pain is the most common cause of office hysteroscopy (OH) failure. There is no consensus on alleviation of pain during OH. The aim was to compare the effectiveness of pain-relieving methods during OH. STUDY DESIGN: A prospective randomized open-label trial included women subjected to OH. All women received 100 mg of ketoprofen intravenously pre-procedure. Women were randomly assigned to 3 arms: A) no local anesthesia, B) infiltration anesthesia with 20 ml of 1% lidocaine solution, C) paracervical block with 20 ml of 1% lidocaine solution. Karl Storz Bettocchi® rigid hysteroscope with a 5 mm operative sheath was used. Intensity of pain in numeric rating scale (NRS), intensity of cervical bleeding, frequency of vasovagal episodes, and failure rate were compared. RESULTS: The study involved 201 women, 67 in each arm. NRS value during OH was higher in arm A than in B and C (6.3 vs. 5.1 vs. 5.0; p = 0.01). NRS value after OH did not differ and in all arms pain was imperceptible (p = 0.007). Cervical bleeding was more frequent in arm B than in A and C (76.1% vs. 33.4% vs. 35.9%; p < 0.0001), but its intensity did not differ from the other arms (p = 0.3). Vasovagal episode was most common in arm B (p = 0.048). There was no difference in the failure rate between the arms (p = 0.08). CONCLUSIONS: The paracervical block, albeit technically the most laborious, has proven to be the most beneficial for the patient in terms of overall comfort and for the surgeon regarding feasibility.

Comparison of dydrogesterone plus progesterone gel with subcutaneous aqueous progesterone plus progesterone gel for luteal phase supplementation of subsequent in vitro cycle in women after previous cycle failure.

OBJECTIVES: The luteal phase supplementation (LPS) of the in vitro fertilization (IVF) cycle is crucial to increase the chance of a live birth. There is no preferred progestogen for use in the general population. The optimal progestogen regimen in the event of prior IVF failure is unknown. The aim was to compare the live birth rate for dydrogesterone plus progesterone gel versus aqueous progesterone plus progesterone gel in LPS of the IVF cycle in women with at least one previous IVF failure. MATERIAL AND METHODS: A prospective randomized single-center study enrolled women with at least one previous IVF failure undergoing another IVF cycle. Women were randomly assigned in a 1:1 ratio to 2 arms depending on LPS protocol: dydrogesterone (Duphaston®) + progesterone in vaginal gel (Crinone®) vs aqueous progesterone solution in subcutaneous injection (Prolutex®) + progesterone in vaginal gel (Crinone®). All women underwent fresh embryo transfer. RESULTS: The live birth rate with one prior IVF failure was 26.9% for D + PG vs 21.2% for AP + PG (p = 0.54), and with at least two IVF failures: 16% for D + PG vs 31.1% for AP + PG (p = 0.16). There were no significant differences in live birth rates between protocols, regardless of the number of prior IVF failures. CONCLUSIONS: In light of the evidence from this study that neither of the two LPS protocols is more effective in women with prior IVF failure, other factors, such as potential side effects, dosing convenience and patient preference, should be considered when choosing a treatment.

Raspberry Leaves and Extracts-Molecular Mechanism of Action and Its Effectiveness on Human Cervical Ripening and the Induction of Labor.

The gestational period is an incredibly stressful time for a pregnant woman. Pregnant patients constantly seek effective and reliable compounds in order to achieve a healthy labor. Nowadays, increasing numbers of women use herbal preparations and supplements during pregnancy. One of the most popular and most frequently chosen herbs during pregnancy is the raspberry leaf (Rubus idaeus). Raspberry extracts are allegedly associated with a positive effect on childbirth through the induction of uterine contractions, acceleration of the cervical ripening, and shortening of childbirth. The history of the consumption of raspberry leaves throughout pregnancy is vast. This review shows the current status of the use of raspberry leaves in pregnancy, emphasizing the effect on the cervix, and the safety profile of this herb. The majority of women apply raspberry leaves during pregnancy to induce and ease labor. However, it has not been possible to determine the exact effect of using raspberry extracts on the course of childbirth and the perinatal period. Additionally, it is unclear whether this herb has only positive effects. The currently available data indicate a weak effect of raspberry leaf extracts on labor induction and, at the same time, their possible negative impact on cervical ripening.

Analysis of RCAS1 immunoreactivity within hydatidiform mole cells and decidual cells according to the applied therapeutic strategy: surgery or surgery followed by chemotherapy.

INTRODUCTION: Trophoblast cells cooperate with both maternal immune cells and decidual cells to help develop the suppressive microenvironment of the endometrium. The maternal immune response against hydatidiform mole depends on this suppressive endometrial profile. Since RCAS1 is one of the molecular factors participating in the development of the suppressive profile of the endometrium we decided to examine the immunoreactivity of the RCAS1 within both the trophoblast and decidual cells during the development of hydatidiform mole. METHODS: We analyzed the immunoreactivity of RCAS1 on both trophoblast and decidual cells derived from patients who underwent curettage because of hydatidiform mole. These patients were then divided into two subgroups according to whether or not they required chemotherapy after the surgical procedure. RESULT: We observed significantly lower immunoreactivity levels of both RCAS1 within the complete molar lesions of the patients on whom surgery alone was performed when compared to the levels found in those for whom surgery was followed by chemotherapy. CONCLUSION: RCAS1 staining may provide information regarding the intensity of the immunosuppressive microenvironment of both the molar lesion and the endometrium. This information can prove significant in determining the clinical course of hydatidiform mole.

[Translabial ultrasonography in pelvic floor prolapse and urinary incontinence diagnostics]. / Przezkroczowa ultrasonograficzna diagnostyka zaburzen statyki narzadu rodnego i nietrzymania moczu.

Technological advances in the construction of sonographic devices and increasingly universal access to such tests considerably widens the range of diagnostic application of the sonographic examination. This situation also refers to pelvic organs prolapse. At present, sonographic sets used in everyday obstetrical-gynecological practice allow for insight into the structures forming the female pelvic floor, and the obtained images constitute a valuable addition to the physical examination. Positioning the sonographic transducer on a the perineum enables to visualize the three compartments of the female pelvis minor. After freezing the image, it is possible to assess the position of anatomical structures in relation to bones and designated surfaces, establish mutual distances and measure appropriate angles. Most information can be obtained in this manner within the range of the frontal compartment, whose damage is often linked with urinary incontinence. The examination standards developed so far, including the analysis of the quantitative parameters, greatly minimize the potential subjectivity of the assessment of the existing disorders. Apart from its low costs, the main value of the sonographic examination of the pelvic floor is the possibility to dynamically assess the changes in statics which take place during functional testing. Not only does it have a cognitive significance, but also it allows to adjust the scope of the surgical correction to the existing damages. Thus, indirectly it can contribute to the reduction of a number of subsequent remedial surgeries. Three-dimensional sonography allows to thoroughly examine the construction and functioning of the anal levators and to detect their possible damage. It is the trauma to these muscles--occurring, among others, during childbirth--that is one of the major causes of pelvic organs descent and prolapse in women. Sonographic examination also enables to visualize the artificial material, the use of which is increasingly frequent in the surgical treatment of pelvic organs prolapse. The remedial kits currently in use are not visible in classic X-ray examinations and CT however, they can be easily visualized by means of a sonographic test. This way it is possible to locate the positioned tapes or meshes and to establish their orientation towards the urethra, the bladder and the anus. It is also possible to observe the complications (e.g. hematomas) following the surgical procedures via the transvaginal access. Transperineal sonography is a relatively inexpensive method that may be performed in almost every ultrasonographic laboratory Its value, approaching the MRI diagnostic value in the assessment of the pelvic floor defects and its low cost, place ultrasonography on the first place among the methods of imaging the pelvic and uro-genital diaphragm. The results of diagnostics of pelvic organs prolapse obtained by placing the sonographic head on the patient's perineum may also help in establishing the changes of the support apparatus for the uterus and the vagina, bladder urethra and perineum during functional testing and, thus, to verify the clinically established degree of the prolapse. It seems, also, that this method may be used during peri-urethral injections of specific substances and post-application follow-up, an increasingly frequently employed method of urinary incontinence treatment.

[The value of three-dimensional multiplanar (MPV) and volume contrast imaging (VCI) in the ultrasound evaluation of endometrial pathology]. / Wartosc trójwymiarowego obrazowania wieloplaszczyznowego (MPV) i kontrastowego (VCI) w ultrasonograficznej ocenie patologii blony sluzowej jamy macicy.

The aging of the women population as well as widespread use of the ultrasound leads to an increased detection of abnormal endometrial characteristics. The aim of this study was to assess the value of three-dimensional ultrasound viewing options: multi-planar view (MPV) and volume contrast imaging (VCI) in the endometrial evaluation. 147 women, referred for endometrial sampling, because of bleeding or an abnormal endometrial two-dimensional ultrasound image were enrolled in the study. Before dilation and curettage, all patients underwent three-dimension ultrasound scans for endometrial thickness measurements and endometrial-myometrial junction assessment. Ultrasound results and the presence of abnormal vaginal bleeding were compared with pathological diagnosis. Sensitivity, specificity, negative predictive value, and positive predictive value for abnormal vaginal bleeding, irregular endometrial-myometrial junction and endometrial thickness were established. Logistic regression model was used to assessed the relationship between the characteristics and the incidence of endometrial pathology. For each of the independent variables odds ratios were calculated. Sensitivity, specificity of the endometrial thickness cut-off 11 mm were 73.8%, 74.4%, for 10.5 mm 76.2%, 69.8% respectively. The irregular endometrial-myometrial junction reached 70.5% sensitivity and 93% specificity. Odds ratios for 10,5 mm cu-off value of the endometrial thickening and irregular E-M junction were calculated: 4.10 [95% CI: 1.14-14.74] and 36.07 [95% CI: 7.10-183.27]. The negative predictive value of any of these parameters did not exceed 70%. The combination of 3D ultrasound parameters and the occurrence of abnormal vaginal bleeding has reached only 53% sensitivity. In the case of connection of two of these three indices, increased sensitivity of 76.9% and specificity of 82.4%. In an unselected group of women in terms of menopausal status and symptoms endometrial thickness measured and the evaluation of endometrial-myometrial junction using 3D ultrasound is less value in predicting the occurrence of endometrial cancer than in 2D and the endometrial volume calculation.

Prevalence of HPV-DNA in Pap smears containing ASC and AGC performed within Population Programme of Prophylaxis and Early Detection of Early Cervical Cancer.

AIM: to assess the incidence of HPV -DNA in women with ASC/AGC compared to patients with normal Pap smears. MATERIAL AND METHODS: The study group consisted of 242 women (207 ASC and 35 AGC cases). The control group counted 200 age-matched women with negative Pap smears. Cervical samples collected from all the participants were tested for the presence of HPV-DNA using the Hybrid Capture-2 test. RESULTS: Total HPV infection was significantly higher in the study than in the control group (43.0% vs.14.0%) (p=0.005). There was no difference in the incidence of HPV -DNA between ASC and AGC groups. Prevalence of HPV-DNA ASC-H was significantly higher in ASC-US group (83.3% vs. 40.5%) (p=0.004). HPV positive endometrial AGC significantly outnumbered HPV positive endocervical AGC (88.9% vs. 26.9%) (p=0.003). Similar trends were observed for the high-risk type of HPV (p<0.001). CONCLUSIONS: The significant difference in HPV -DNA incidence between the study and control groups suggests that HPV plays a role in the development of ASC and AGC. The implementation of HPV testing in all women diagnosed with ASC or AGC can lead to tailored therapeutic management and more careful follow-up care.

Signaling Pathways Regulating Human Cervical Ripening in Preterm and Term Delivery.

At the end of gestation, the cervical tissue changes profoundly. As a result of these changes, the uterine cervix becomes soft and vulnerable to dilation. The process occurring in the cervical tissue can be described as cervical ripening. The ripening is a process derivative of enzymatic breakdown and inflammatory response. Therefore, it is apparent that cervical remodeling is a derivative of the reactions mediated by multiple factors such as hormones, prostaglandins, nitric oxide, and inflammatory cytokines. However, despite the research carried out over the years, the cellular pathways responsible for regulating this process are still poorly understood. A comprehensive understanding of the entire process of cervical ripening seems crucial in the context of labor induction. Greater knowledge could provide us with the means to help women who suffer from dysfunctional labor. The overall objective of this review is to present the current understanding of cervical ripening in terms of molecular regulation and cell signaling.

CD133 Expression in the Nucleus Is Associated with Endometrial Carcinoma Staging and Tumor Angioinvasion.

BACKGROUND: (1) Endometrial cancer is one of the most common cancers affecting women, with a growing incidence. To better understand the different behaviors associated with endometrial cancer, it is necessary to understand the changes that occur at a molecular level. CD133 is one of the factors that regulate tumor progression, which is primarily known as the transmembrane glycoprotein associated with tumor progression or cancer stem cells. The aim of our study was to assess the impact of subcellular CD133 expression on the clinical course of endometrial cancer. (2) Methods: CD133 expression in the plasma membrane, nucleus, and cytoplasm was assessed by immunohistochemical staining in a group of 64 patients with endometrial cancer representing FIGO I-IV stages, grades 1-3 and accounting for tumor angioinvasion. (3) Results: Nuclear localization of CD133 expression was increased in FIGO IB-IV stages compared to FIGO IA. Furthermore, CD133 expression in the nucleus and plasma membrane is positively and negatively associated with a higher grade of endometrial cancer and angioinvasion, respectively. (4) Conclusions: Our findings suggest that positive nuclear CD133 expression in the tumor may be related to a less favorable prognosis of endometrial carcinoma patients and has emerged as a useful biomarker of a high-risk group.

Low Expression of miR-375 and miR-190b Differentiates Grade 3 Patients with Endometrial Cancer.

Endometrial cancer (EC) is treated according to the stage and prognostic risk factors. Most EC patients are in the early stages and they are treated surgically. However some of them, including those with high grade (grade 3) are in the intermediate and high intermediate prognostic risk groups and may require adjuvant therapy. The goal of the study was to find differences between grades based on an miRNA gene expression profile. Tumor samples from 24 patients with grade 1 (n = 10), 2 (n = 7), and 3 (n = 7) EC were subjected to miRNA profiling using next generation sequencing. The results obtained were validated using the miRNA profile of 407 EC tumors from the external Cancer Genome Atlas (TCGA) cohort. We obtained sets of differentially expressed (DE) miRNAs with the largest amount between G2 to G1 (50 transcripts) and G3 to G1 (40 transcripts) patients. Validation of our results with external data (TCGA) gave us a reasonable gene overlap of which we selected two miRNAs (miR-375 and miR190b) that distinguish the high grade best from the low grade EC. Unsupervised clustering showed a high degree of heterogeneity within grade 2 samples. MiR-375 as well as 190b might be useful to create grading verification test for high grade EC. One of the possible mechanisms that is responsible for the high grade is modulation by virus of host morphology or physiology.

Metastatic and non-metastatic sentinel inguinofemoral lymph nodes in vulvar cancer show an increased lymphangiogenesis.

INTRODUCTION AND OBJECTIVE: Lymph node involvement is a strong predictor of disease recurrence and patient survival in vulvar cancer. The aim of the study was to evaluate the feasibility of sentinel lymph node (SLN) screening, the incidence of skip metastases, and lymph node lymphangiogenesis. MATERIAL AND METHODS: Fifty-five patients participated in this prospective, single centre study. A double SLN screening method was employed using radiocolloid (technetium-99 sulfur colloid) and 1.0% Isosulfan Blue. Immunohistochemistry, using a mouse monoclonal antibody against D2-40, was used to evaluate lymphatic vessel density (LVD). All calculations were performed using STATISTICA software v. 10 (StatSoft, USA, 2011); p < 0.05 was considered significant. RESULTS: Using both methods of SLN detection, 100% accuracy was achieved, and skip metastases were diagnosed in only one woman (1.82%). Peri-tumour median LVD was significantly increased compared with matched intra-tumour samples (p < 0.001), while median LVD was significantly lower in negative, compared with positive SLN, regardless of whether matched non-SLN were negative (p < 0.001) or positive (p = 0.005). Metastatic SLN exhibited significantly higher median LVD compared with matched negative non-SLN (p = 0.015), while no significant difference in median LVD was detected between positive SLN and matched positive non-SLN. However, negative SLN had a significantly higher median LVD compared with matched negative non-SLN (p = 0.012). CONCLUSIONS: SLN detection is a safe and feasible procedure in vulvar cancer. In patients without nodular involvement, SLN, compared with non-SLN, exhibited significantly higher median LVD, which may be an indication of its preparation to host metastases, and thus requires further investigation.

SOX-2, but not Oct4, is highly expressed in early-stage endometrial adenocarcinoma and is related to tumour grading.

BACKGROUND: Expression of SOX-2 and Oct4 as markers for the identification of cancer stem cells (CSCs) has been revealed in several malignancies. In this study, the co-expression of SOX-2 and Oct4 and their correlation with clinicopathological features of endometrial adenocarcinomas (EACs) was investigated. METHODS: SOX-2 and Oct4 expression was assessed by immunohistochemistry in 27 (39.13%) stage IA and in 42 (60.87%) stage IB International Federation of Gynaecology and Obstetrics (FIGO) EACs and related to the clinicopathological features of patients. RESULTS: The expression of SOX-2 was confirmed in 62/69 tumour specimens compared to Oct4 expression in 46/69 specimens (P = 0.015) and no difference in median staining intensity between SOX-2 and Oct-4 was observed. The highest median SOX-2 expression was found in high-grade (G3) EAC samples compared to moderate-grade (G2) EAC specimens (P = 0.020) and low-grade (G1) specimens (P = 0.008), while no differences in median Oct4 expression in EAC samples according to grading were present. In G3 specimens, significantly higher median SOX-2 expression was noted compared to Oct4 (P = 0.002). SOX-2 and Oct4 co-expression was observed only in G1 EAC (R: 0.51; P = 0.031). Age of EAC diagnosis was positively correlated with SOX-2 expression (b = 0.193; R(2) = 10.83%; P = 0.003) but not to age of menarche, menopause, parity or body mass index. CONCLUSIONS: There is no need to use SOX-2 expression as a poor outcome predictor in stage I EAC, and SOX-2 expression should be analysed in more advanced stages.