Why Does Your Uterus Become Malignant? The Impact of the Microbiome on Endometrial Carcinogenesis.

The aim of this review was to describe the uterine microbiome composition that has been analyzed so far and describe potential pathways in the carcinogenesis of the endometrium. The microbiome in the uterine environment is involved in apoptosis and proliferation during the menstruation cycle, pregnancy maintenance, and immune system support. However, bacteria in the uterus could stimulate inflammation, which when chronic results in malignancy. An altered gut microbiota initiates an inflammatory response through microorganism-associated molecular patterns, which leads to intensified steroidogenesis in the ovaries and cancers. Moreover, intestinal bacteria secreting the enzyme ß-glucuronidase may increase the level of circulating estrogen and, as a result, be influential in gynecological cancers. Both the uterine and the gut microbiota play a pivotal role in immune modulation, which is why there is a demand for further investigation from both the diagnostic and the therapeutic perspectives.

Common Variants in One-Carbon Metabolism Genes (MTHFR, MTR, MTHFD1) and Depression in Gynecologic Cancers.

We investigated the association between methylenetetrahydrofolate reductase (gene MTHFR 677C>T, rs1801133), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR 2756A>G, rs1805087), and methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 (gene MTHFD1 1958G>A, rs2236225)-well-studied functional variants involved in one-carbon metabolism-and gynecologic cancer risk, and the interaction between these polymorphisms and depression. A total of 200 gynecologic cancer cases and 240 healthy controls were recruited to participate in this study. Three single-nucleotide variants (SNVs) (rs1801133, rs1805087, rs2236225) were genotyped using the PCR-restriction fragment length polymorphism method. Depression was assessed in all patients using the Hamilton Depression Scale. Depression was statistically significantly more frequent in women with gynecologic cancers (69.5% vs. 34.2% in controls, p < 0.001). MTHFD1 rs2236225 was associated with an increased risk of gynecologic cancers (in dominant OR = 1.53, p = 0.033, and in log-additive models OR = 1.37, p = 0.024). Moreover, an association was found between depression risk and MTHFR rs1801133 genotypes in the controls but not in women with gynecologic cancers (in codominant model CC vs. TT: OR = 3.39, 95%: 1.49-7.74, p = 0.011). Cancers of the female reproductive system are associated with the occurrence of depression, and ovarian cancer may be associated with the rs2236225 variant of the MTHFD1 gene. In addition, in healthy aging women in the Polish population, the rs1801133 variant of the MTHFR gene is associated with depression.

Correction: Pakula et al. Deciphering the Molecular Mechanism of Spontaneous Senescence in Primary Epithelial Ovarian Cancer Cells. Cancers 2020, 12, 296.

In the original publication [...].

Differential Expression of HIF1A, EPAS1, and VEGF Genes in Benign and Malignant Ovarian Neoplasia.

Ovarian cancer (OC) has the highest mortality rate of all gynecological malignancies. Moreover, at the time of the first clinical manifestation, most patients have an advanced stage of the disease. Our study examined differences in mRNA levels of hypoxia-inducible factor 1-alpha (HIF1A); endothelial PAS domain protein 1, also known as hypoxia-inducible factor 2-alpha (HIF2A/EPAS1); and vascular endothelial growth factor A (VEGFA) between cancerous tissue, benign hyperplastic changes in the ovary, and normal tissue. Our cohorts consisted of 52 patients diagnosed with OC (n = 55), benign non-cancerous changes (n = 21), and normal tissue samples (n = 38). The mRNA expression level was evaluated using RT-qPCR. We found that gene expression changes were visible not only in the case-control study, but also along with changes in severity. Additionally, the gene expression was differentiated in age, BMI, menopausal status, and the number of comorbidy-related groups. Furthermore, our findings demonstrate that analyzing the correlation between genes is essential. In a case-to-case and case-to-control study, we observed disturbances in the expression levels of interdependent genes. Our findings suggest that mutual association in the expression of both HIF1A and HIF2A/EPAS1 with VEGFA has prognostic importance for patients with OC. Our observations may help identify patients for clinical trials aimed at inhibiting the hypoxia-induced neovascularization-dependent pathways.

A Unique Glassy Cell Carcinoma (GCC) of the Cervix Diagnosed during Pregnancy-A Case Report.

Glassy Cell carcinoma (GCC) of the cervix is classified as a unique, aggressive neoplasm, with different sensitivity to chemotherapy and radiotherapy. It is such an extremely rare tumor that it is practically not observed during pregnancy. Information on the coexistence of cervical GCC with pregnancy is also unique, so it seems extremely important to disseminate it in order to develop the most effective treatment regimen. Additionally, making any decisions regarding therapeutic methods during pregnancy encounters great ethical problems. We present the case of a 26-year-old pregnant woman, 18 weeks gestation, diagnosed with GCC of the cervix, IB3 grade in the International Federation of Gynecology and Obstetrics (FIGO) scale. Despite the unfavorable prognosis, the use of chemotherapy in a pregnant patient brought on a favorable therapeutic effect, without any negative effects on the fetus. The article also presents a literature review on the epidemiology, pathology, immunohistochemistry, treatment and prognosis of this rare disease.

A Rare Case of HELLP Syndrome with Hematomas of Spleen and Liver, Eclampsia, Severe Hypertension and Prolonged Coagulopathy-A Case Report.

The HELLP syndrome (hemolysis, liver damage and thrombocytopenia) is a rare (0.5−0.9%) but serious complication of pregnancy or puerperium associated with a higher risk of maternal and fetal mortality and morbidity. Liver and spleen hematomas rarely entangle (<2%) HELLP cases, but rupture of the hematomas presents an immediate threat to life. We present the history of a 35-year old pregnant woman (at the 31st week) admitted to our hospital due to the risk of premature delivery. On the first day, the patient did not report any complains, and the only abnormality was thrombocytopenia 106 G/L. However, within several hours, tests showed platelet levels of 40.0 G/L, LDH 2862.0 U/L and AST 2051.6 U/L, and the woman was diagnosed with severe HELLP syndrome, complicated by hematomas of the liver and spleen, seizures (eclampsia), severe arterial hypertension and coagulation disorders. The purpose of this article is to highlight the need for early investigation of the causes of thrombocytopenia and the differentiation of HELLP from other thrombotic microangiopathies (TMAs).

Identification of New Molecular Biomarkers in Ovarian Cancer Using the Gene Expression Profile.

Ovarian cancer is a common cause of death among women worldwide. The current diagnostic and prognostic procedures available for the treatment of ovarian cancer are either not specific or are very expensive. Gene expression profiling has proved to be a very effective tool in the exploration of new molecular markers in patients with ovarian cancer, although the link between such markers and patient survival and clinical outcomes is still elusive. We are looking for genes that may function in the development and progression of ovarian cancer. The aim of our study was to evaluate the expression of selected suppressor genes (ATM, BRCA1, BRCA2), proto-oncogenes (KRAS, c-JUN, c-FOS), pro-apoptotic genes (NOXA, PUMA), genes related to chromatin remodeling (MEN1), and genes related to carcinogenesis (NOD2, CHEK2, EGFR). Tissue samples from 30 normal ovaries and 60 ovarian carcinoma tumors were provided for analysis of the gene and protein expression. Gene expression analysis was performed using the real-time PCR method. The protein concentrations from tissue homogenates were determined using the ELISA technique according to the manufacturers' protocols. An increase in the expression level of mRNA and protein in women with ovarian cancer was observed for KRAS, c-FOS, PUMA, and EGFR. No significant changes in the transcriptional levels we observed for BRCA1, BRCA2, NOD2, or CHEK2. In conclusion, we suggest that KRAS, NOXA, PUMA, c-FOS, and c-JUN may be associated with poor prognosis in ovarian cancer.

Progressing Vulvar Melanoma Caused by Instability in cKIT Juxtamembrane Domain: A Case Report and Review of Literature.

In order to identify the molecular pathways governing melanoma and track its progression, the next-generation sequencing (NGS) approach and targeted sequencing of cancer genes were employed. The primary tumor, as well as metastatic tissue, of an 84-year-old patient diagnosed with vulvar melanoma (VM), were investigated. The primary tumor specimen showed multiple somatic mutations in TP53 gene, suggesting its major contribution to melanoma origin. The metastatic sample showed additional alterations, including other melanoma-related genes. Clinical relevancy is postulated to juxtamembrane region instability of KIT gene (c-KIT). We did not identify BRAF or NRAS alterations, which are typical for the most common melanoma pathway-MAPK cascade. However, it should be noted that this is the first report evidencing PDGFRA in melanoma, although its role in triggering VM needs to be further elucidated.

Using a Modified Polysaccharide as a Hemostatic Agent Results in Less Reduction of the Ovarian Reserve after Laparoscopic Surgery of Ovarian Tumors-Prospective Study.

Background and Objectives: The study investigated whether the method of achieving hemostasis affects the ovarian reserve in patients undergoing laparoscopic surgery due to ovarian tumors or cysts. Materials and Methods: Patients with unilateral tumors or ovarian cysts, who qualified for laparoscopic tumor enucleation, were randomly selected to receive modified polysaccharides or bipolar coagulation. Ovarian reserve was analyzed by anti-Mullerian hormone (AMH) level. Results: The study included 38 patients: 19 patients in the modified polysaccharide group and 19 in the bipolar coagulation group. Patients after bipolar coagulation treatment had statistically significantly lower AMH 6 months after surgery compared to the group treated with modified starch. The levels of AMH in the study and control groups were 3.96 +/- 2.12 vs. 2.51 +/- 1.39 ng/mL, respectively; p = 0.018. A statistically significant decrease in AMH was also demonstrated in the bipolar coagulation group as compared to the preoperative assessment (p = 0.049). There was no statistically significant decrease in AMH in the group of patients treated with the modified starch. Conclusions: Using a modified polysaccharide during laparoscopic cystectomy is effective and has a positive effect on the ovarian reserve compared to the use of bipolar coagulation. Both the AMH level 6 months after surgery and the percentage decrease in AMH were more favorable in the group of patients treated with modified starch.

Altered Expression of ESR1, ESR2, PELP1 and c-SRC Genes Is Associated with Ovarian Cancer Manifestation.

Ovarian cancer remains the leading cause of death due to gynecologic malignancy. Estrogen-related pathways genes, such as estrogen receptors (ESR1 and ESR2) and their coregulators, proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), and proto-oncogene tyrosine-protein kinase c-Src (SRC) are involved in ovarian cancer induction and development, still they require in-depth study. In our study, tissue samples were obtained from 52 females of Caucasian descent (control group without cancerous evidence (n = 27), including noncancerous benign changes (n = 15), and the ovarian carcinoma (n = 25)). Using quantitative analyses, we investigated ESRs, PELP1, and SRC mRNA expression association with ovarian tumorigenesis. Proteins' presence and their location were determined by Western blot and immunohistochemistry. Results showed that PELP1 and SRC expression levels were found to differ in tissues of different sample types. The expression patterns were complex and differed in the case of ovarian cancer patients compared to controls. The most robust protein immunoreactivity was observed for PELP1 and the weakest for ESR1. The expression patterns of analyzed genes represent a potentially interesting target in ovarian cancer biology, especially PELP1. This study suggests that specific estrogen-mediated functions in the ovary and ovary-derived cancer might result from different local interactions of estrogen with their receptors and coregulators.

Smoking and Smoking Cessation in the Risk for Fetal Growth Restriction and Low Birth Weight and Additive Effect of Maternal Obesity.

Many studies have shown that neonates of smoking mothers have a lower birth weight, but several issues remain poorly studied, e.g., the effects of giving up smoking or the combined effects of smoking and maternal obesity. Therefore, we evaluated a prospective cohort of 912 mothers in a single pregnancy, recruited in Poland, in 2015-2016. In the cohort, we recorded 72 (7.9%) newborns with birth weight <10th percentile, 21 (2.3%) fetal growth restriction (FGR) cases, and 60 (6.6%) low birth weight (LBW, <2500 g) newborns. In the cohort, 168 (18.4%) women smoked before pregnancy; the mean number of cigarettes/day was 10.8 (1-30), and the mean number of years of cigarette smoking was 8.5 (1-25). Among smokers, 57 (6.3%) women smoked in the first trimester. Adjusted odds ratio (AOR) of newborn outcomes (with 95% confidence intervals, CI) was calculated in multi-dimensional logistic regressions. Compared to participants who had never smoked, smoking before pregnancy was associated with a higher odds ratio of birth weight <10th percentile (AOR = 1.93, CI: 1.08-3.44, p = 0.027), but the result for LBW (AOR = 2.76, CI: 1.05-7.26, p = 0.039) and FGR (AOR = 1.13, CI: 0.38-3.36, p = 0.822) had the wider confidence interval or was insignificant. Effects of smoking cessation before pregnancy were statistically insignificant for the studied outcomes. Smoking in the first trimester was associated with a higher risk of birth weight <10th percentile (AOR = 4.68, CI: 2.28-9.62, p < 0.001), LBW (AOR = 6.42, CI: 1.84-22.36, p = 0.004), and FGR (AOR = 3.60, CI: 0.96-13.49, p = 0.057). Smoking cessation in the second/third trimester was associated with a higher odds ratio of birth weight <10th percentile (AOR = 4.54, CI: 1.58-13.02, p = 0.005), FGR (AOR = 3.36, CI: 0.6-18.74, p = 0.167), and LBW (AOR = 2.14, CI: 0.62-7.36), p = 0.229), to a similar degree to smoking in the first trimester. The odds ratios were higher in the subgroup of pre-pregnancy body mass index ≥25 kg/m2 for the risk of birth weight <10th percentile (AOR = 6.39, CI: 2.01-20.34, p = 0.002) and FGR (AOR = 6.25, CI: 0.86-45.59, p = 0.071). The length of cigarette smoking time was also the risk factor for studied outcomes. Conclusions: Smoking in the first trimester increased the studied risks, and the coexistence of excessive maternal weight increased the effects. Smoking cessation during the second/third trimester did not have a protective effect.

Pre-Pregnancy Obesity vs. Other Risk Factors in Probability Models of Preeclampsia and Gestational Hypertension.

In the face of the obesity epidemic around the world, attention should be focused on the role of maternal obesity in the development of pregnancy. The purpose of this analysis was to evaluate the prediction of preeclampsia (PE) and isolated gestational hypertension (GH) for a number of maternal factors, in order to investigate the importance of pre-pregnancy obesity (body mass index, BMI ≥ 30 kg/m2), compared to other risk factors (e.g., prior PE, pregnancy weight gain (GWG), infertility treatment, interpregnancy interval, family history, the lack of vitamin supplementation, urogenital infection, and socioeconomic factors). In total, 912 women without chronic diseases were examined in a Polish prospective cohort of women with a single pregnancy (recruited in 2015-2016). Separate analyses were performed for the women who developed GH (n = 113) vs. 775 women who remained normotensive, as well as for those who developed PE (n = 24) vs. 775 controls. The probability of each disease was assessed for the base prediction model (age + primiparity) and for the model extended by one (test) variable, using logistic regression. Three measures were used to assess the prediction: area under curve (AUC) of the base and extended model, integrated discrimination improvement (IDI) (the index shows the difference between the value of the mean change in the predicted probability between the group of sick and healthy women when a new factor is added to the model), and net reclassification improvement (NRI) (the index focuses on the reclassification table describing the number of women in whom an upward or downward shift in the disease probability value occurred after a new factor had been added, including results for healthy and sick women). In the GH prediction, AUC increased most strongly when we added BMI (kg/m2) as a continuous variable (AUC = 0.716, p < 0.001) to the base model. The highest IDI index was obtained for prior GH/PE (IDI = 0.068, p < 0.001). The addition of BMI as a continuous variable or BMI ≥ 25 kg/m2 improved the classification for healthy and sick women the most (NRI = 0.571, p < 0.001). In the PE prediction, AUC increased most strongly when we added BMI categories (AUC = 0.726, p < 0.001) to the base model. The highest IDI index was obtained for prior GH/PE (IDI = 0.050, p = 0.080). The addition of BMI categories improved the classification for healthy and sick women the most (NRI = 0.688; p = 0.001). After summing up the results of three indexes, the probability of hypertension in pregnancy was most strongly improved by BMI, including BMI ≥ 25 kg/m2 for the GH prediction, and BMI ≥ 30 kg/m2 for the PE prediction. Main conclusions: Pre-pregnancy BMI was the most likely factor to increase the probability of developing hypertension in pregnancy, compared to other risk factors. Hierarchies of PE and GH risk factors may suggest different (or common) mechanisms of their development.

The Influence of Maternal BMI on Adverse Pregnancy Outcomes in Older Women.

As mothers age, the risk of adverse pregnancy outcomes may increase, but the results so far are controversial and several issues remain unknown, such as the impact of maternal weight on the effects associated with older age. In a prospective cohort of 912 Polish women with singleton pregnancies (recruited in 2015-2016), we assessed the pregnancy outcomes depending on the mother's age (18-24, 25-29, 30-34, 35-39, and ≥40 years). Women aged ≥35 years (vs. <35 years) were assessed in terms of body mass index (BMI). Multidimensional logistic regression was used to calculate the odds ratios (with 95% confidence intervals) of the pregnancy results. The risk profiles (using the Lowess method) were applied to determine the threshold risk. We found that both the youngest and the oldest group members displayed higher adjusted odds ratios of preeclampsia (PE), intrauterine growth restriction (IUGR), and preterm birth <37th week (U-shaped risk). In the remaining cases, the age ≥40 years, compared to the youngest age 18-24 years, was associated with a higher adjusted risk of gestational hypertension (GH) (AOR = 5.76, p = 0.034), gestational diabetes mellitus GDM-1 (AOR = 7.06, p = 0.016), cesarean section (AOR = 6.97, p <0.001), and low birth weight LBW (AOR = 15.73, p = 0.033) as well as macrosomia >4000 g (AOR = 8.95, p = 0.048). We found that older age ≥35 years (vs. <35 years) was associated with higher adjusted odds ratios of all the pregnancy outcomes investigated. In obese women, these adverse older age related results were found to be more intense in GH study, as well as (though weaker) in birth <37th week study, small-for-gestational age birth weight (SGA), LBW, large-for-gestational age birth weight (LGA), and macrosomia. In overweight women, these adverse older age related results were found to be more intense in preterm birth study, as well as (though weaker) in SGA and LBW. In underweight women, adverse pregnancy outcomes related to older age were more intense in a study of cesarean section. At the same time, underweight was associated with reversal of some negative effects of older age (we found lower odds ratios of GDM-1 diabetes). The maternal threshold age above which the risk of GH, PE, GDM, caesarean section, and preterm birth increased was 33-34 years (lower than the threshold of 35 years assumed in the literature), and the threshold risk of IUGR, LBW, SGA, LGA, and macrosomia was 36-37 years. Main conclusions: Older maternal age was associated with a higher chance of all kinds of obstetric complications. Older women should particularly avoid obesity and overweight.

Pre-Pregnancy Obesity, Excessive Gestational Weight Gain, and the Risk of Pregnancy-Induced Hypertension and Gestational Diabetes Mellitus.

Excessive pre-pregnancy weight is a known risk factor of pregnancy complications. The purpose of this analysis was to assess the relationship between several categories of maternal weight and the risk of developing hypertension and diabetes in pregnancy, and the relationship of these complications with the results of the newborn. It was carried out in a common cohort of pregnant women and taking into account the influence of disturbing factors. Our analysis was conducted in a prospective cohort of 912 Polish pregnant women, recruited during 2015-2016. We evaluated the women who subsequently developed diabetes with dietary modification (GDM-1) (n = 125) and with insulin therapy (GDM-2) (n = 21), as well as the women who developed gestational hypertension (GH) (n = 113) and preeclampsia (PE) (n = 24), compared to the healthy controls. Odds ratios of the complications (and confidence intervals (95%)) were calculated in the multivariate logistic regression. In the cohort, 10.8% of the women had pre-pregnancy obesity (body mass index (BMI) ≥ 30 kg/m2), and 36.8% had gestational weight gain (GWG) above the range of the Institute of Medicine recommendation. After correction for excessive GWG and other confounders, pre-pregnancy obesity (vs. normal BMI) was associated with a higher odds ratio of GH (AOR = 4.94; p < 0.001), PE (AOR = 8.61; p < 0.001), GDM-1 (AOR = 2.99; p < 0.001), and GDM-2 (AOR = 11.88; p <0.001). The threshold risk of development of GDM-2 occurred at lower BMI values (26.9 kg/m2), compared to GDM-1 (29.1 kg/m2). The threshold point for GH was 24.3 kg/m2, and for PE 23.1 kg/m2. For GWG above the range (vs. GWG in the range), the adjusted odds ratios of GH, PE, GDM-1, and GDM-2 were AOR = 1.71 (p = 0.045), AOR = 1.14 (p = 0.803), AOR = 0.74 (p = 0.245), and AOR = 0.76 (p = 0.672), respectively. The effect of maternal edema on all the results was negligible. In our cohort, hypertension and diabetes were associated with incorrect birth weight and gestational age at delivery. Conclusions: This study highlights the importance and influence of excessive pre-pregnancy maternal weight on the risk of pregnancy complications such as diabetes and hypertension which can impact fetal outcomes.

First Trimester Microelements and their Relationships with Pregnancy Outcomes and Complications.

Microelements involved in the oxidative balance have a significant impact on human health, but their role in pregnancy are poorly studied. We examined the relationships between first trimester levels of selenium (Se), iron (Fe), zinc (Zn), and copper (Cu), as well as maternal characteristics and pregnancy results. The data came from a Polish prospective cohort of women in a single pregnancy without chronic diseases. A group of 563 women who had a complete set of data, including serum microelements in the 10-14th week was examined, and the following were found: 47 deliveries <37th week; 48 cases of birth weight <10th and 64 newborns >90th percentile; 13 intrauterine growth restriction (IUGR) cases; 105 gestational hypertension (GH) and 15 preeclampsia (PE) cases; and 110 gestational diabetes mellitus (GDM) cases. The microelements were quantified using mass spectrometry. The average concentrations (and ranges) of the elements were as follows: Se: 60.75 µg/L (40.91-125.54); Zn: 618.50 µg/L (394.04-3238.90); Cu: 1735.91 µg/L (883.61-3956.76); and Fe: 1018.33 µg/L (217.55-2806.24). In the multivariate logistic regression, we found that an increase in Se of 1 µg/L reduces the risk of GH by 6% (AOR = 0.94; p = 0.004), the risk of IUGR by 11% (AOR = 0.89; p = 0.013), and the risk of birth <34th week by 7% (but close to the significance) (AOR = 0.93; p = 0.061). An increase in Fe of 100 µg/L reduces the risk of PE by 27% (AOR = 0.73; p = 0.009). In the multivariable linear regression, we found negative strong associations between prepregnancy BMI, Se (ß = -0.130; p = 0.002), and Fe (ß = -0.164; p < 0.0001), but positive associations with Cu (ß = 0.320; p < 0.000001). The relationships between Se and maternal age (ß = 0.167; p < 0.0001), Se and smoking (ß = -0.106; p = 0.011) and Cu, and gestational age from the 10-14th week (ß = 0.142; p < 0.001) were also found. Secondary education was associated with Zn (ß = 0.132; p = 0.004) and higher education was associated with Cu (ß = -0.102; p = 0.023). A higher financial status was associated with Fe (ß = 0.195; p = 0.005). Other relationships were statistically insignificant. Further research is needed to clarify relationships between first trimester microelements and pregnancy complications. In addition, attention should be paid to lifestyle-related and socioeconomic factors that affect microelement levels.

Deciphering the Molecular Mechanism of Spontaneous Senescence in Primary Epithelial Ovarian Cancer Cells.

Spontaneous senescence of cancer cells remains a puzzling and poorly understood phenomenon. Here we comprehensively characterize this process in primary epithelial ovarian cancer cells (pEOCs). Analysis of tumors from ovarian cancer patients showed an abundance of senescent cells in vivo. Further, serially passaged pEOCs become senescent after a few divisions. These senescent cultures display trace proliferation, high expression of senescence biomarkers (SA--Gal, -H2A.X), growth-arrest in the G1 phase, increased level of cyclins D1, D2, decreased cyclin B1, up-regulated p16, p21, and p53 proteins, eroded telomeres, reduced activity of telomerase, predominantly non-telomeric DNA damage, activated AKT, AP-1, and ERK1/2 signaling, diminished JNK, NF-B, and STAT3 pathways, increased formation of reactive oxygen species, unchanged activity of antioxidants, increased oxidative damage to DNA and proteins, and dysfunctional mitochondria. Moreover, pEOC senescence is inducible by normal peritoneal mesothelium, fibroblasts, and malignant ascites via the paracrine activity of GRO-1, HGF, and TGF-1. Collectively, pEOCs undergo spontaneous senescence in a mosaic, telomere-dependent and telomere-independent manner, plausibly in an oxidative stress-dependent mechanism. The process may also be activated by extracellular stimuli. The biological and clinical significance of pEOC senescence remains to be explored.

Performance of Selected Models for Predicting Malignancy in Ovarian Tumors in Relation to the Degree of Diagnostic Uncertainty by Subjective Assessment With Ultrasound.

OBJECTIVES: The study's main aim was to evaluate the relationship between the performance of predictive models for differential diagnoses of ovarian tumors and levels of diagnostic confidence in subjective assessment (SA) with ultrasound. The second aim was to identify the parameters that differentiate between malignant and benign tumors among tumors initially diagnosed as uncertain by SA. METHODS: The study included 250 (55%) benign ovarian masses and 201 (45%) malignant tumors. According to ultrasound findings, the tumors were divided into 6 groups: certainly benign, probably benign, uncertain but benign, uncertain but malignant, probably malignant, and certainly malignant. The performance of the risk of malignancy index, International Ovarian Tumor Analysis assessment of different neoplasias in the adnexa model, and International Ovarian Tumor Analysis logistic regression model 2 was analyzed in subgroups as follows: SA-certain tumors (including certainly benign and certainly malignant) versus SA-probable tumors (probably benign and probably malignant) versus SA-uncertain tumors (uncertain but benign and uncertain but malignant). RESULTS: We found a progressive decrease in the performance of all models in association with the increased uncertainty in SA. The areas under the receiver operating characteristic curve for the risk of malignancy index, logistic regression model 2, and assessment of different neoplasias in the adnexa model decreased between the SA-certain and SA-uncertain groups by 20%, 28%, and 20%, respectively. The presence of solid parts and a high color score were the discriminatory features between uncertain but benign and uncertain but malignant tumors. CONCLUSIONS: Studies are needed that focus on the subgroup of ovarian tumors that are difficult to classify by SA. In cases of uncertain tumors by SA, the presence of solid components or a high color score should prompt a gynecologic oncology clinic referral.

Ovarian steroid cell tumor as an example of severe hyperandrogenism in 45-year-old woman.

Approximately, 5% of ovarian tumors have hormonal activity. Steroid cell tumors (SCTs) represent about 0.1% of all ovarian tumors. They cause hyperandrogenism associated with typical virilization. In this case report, we present 45-year-old women with unmalignant ovarian SCT-producing androgens which cause severe virilization and secondary amenorrhea lasting two years. Transvaginal ultrasound, computed tomography of adrenal glands, magnetic resonance imaging of small pelvis, laboratory tests (including serum concentration of FSH, LH, testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEA-S), as well as ROMA index) were performed. During hormonal evaluation, elevated concentrations of serum T - on admission 1.72 ng/ml and one month later 3.75 ng/ml (normal range 0.08-0.82 ng/ml) and A - 24.90 ng/ml (normal range 0.40-3.40 ng/ml) were found. The ROMA index was within the normal range. Enlargement of the left ovary by solid mass 56 × 43 mm was found during ultrasound examination. Based on small pelvis MRI scan and hormonal finding, patient was qualified for laparotomy. During this procedure, the left salpingo-oophorectomy with removal of the tumor was performed. The histopathological examination identified SCT. During follow-up examination, one day after surgery, we found serum testosterone levels within normal ranges - 0.74 ng/ml (normal range 0.08-0.82 ng/ml). This case shows that hormone-producing ovarian tumors are rare but very important clinical causes of severe hyperandrogenism.

First Trimester Serum Copper or Zinc Levels, and Risk of Pregnancy-Induced Hypertension.

Early identification of women at risk of developing pregnancy-induced hypertension (PIH) is very important. The involvement of copper (Cu) and zinc (Zn) in the oxidative balance suggests the possibility of their association with this disease, in which oxidative stress plays a key role. However, it has not been established so far whether the microelement levels in early pregnancy may be risk markers of the disease, as prospective studies are limited in number. In our innovative single-center study, we identified from a prospective cohort of healthy women in the 10-14th week of a single pregnancy: women subsequently developing pregnancy-induced hypertension (n = 121) and matched women remaining normotensive (n = 363). We measured the concentrations of microelements in the serum from 10-14 week, using the inductively coupled plasma mass spectrometry (ICP-MS). The odds ratios of the disease (and 95% confidence intervals) were assessed in logistic regression. In the whole cohort, the odds ratio (OR) of PIH was 1.52 (p = 0.174) for women in the lowest (Q1) quartile of Cu (≤1540.58 µg/L) compared with women in the highest (Q4) quartile (>1937.46 µg/L), but adjusted odds ratio (AOR) was 2.17 (p = 0.019) after adjusted for pre-pregnancy body mass index (BMI) and gestational age at recruitment. The higher levels of Cu in the subgroup of BMI ≥ 25 kg/m2 compared to normal BMI were found (1847.64 vs. 1673.36 µg/L; p < 0.0001). In the subgroup of women with the normal pre-pregnancy BMI, the adjusted odds ratio of PIH was AOR = 2.95 (p = 0.040) for Q1 vs. Q4 quartile. Our results suggest that lower Cu levels in early pregnancy may be connected with higher risk of PIH, but BMI affected estimated odds ratios. Zinc levels had no effect on the risk.

The Role of Early Pregnancy Maternal Selenium Levels on the Risk for Small-for-Gestational Age Newborns.

It has not yet been established, whether or not the maternal serum selenium (Se) in early pregnancy may be a risk marker of small-for-gestational age (SGA) birth weight. Selenium is important for human health and is involved in oxidative balance, a key element in the development of the placenta and fetus. This innovative study was nested in a prospective cohort of 750 women recruited in the 10-14th week of a single pregnancy, all of whom were healthy during recruitment. We examined mothers delivering SGA infants (with birth weight <10th percentile) (n = 48) and matched mothers delivering appropriate-for-gestational age (AGA) infants (between 10-90th percentile) (n = 192). We measured the maternal microelement concentrations in the serum from the 10-14th gestational week, using the inductively coupled plasma mass spectrometry (ICP-MS). The odds ratios of SGA (and 95% confidence intervals) were assessed in logistic regression. The mean maternal Se concentrations were lower in mothers in the SGA group compared to the AGA group (59.60 vs. 62.54 µg/L; p = 0.020). Women in the lowest Q1 quartile of Se (≤56.60 µg/L) have about three times higher risk of SGA compared to women in the higher quartiles (Q2 or Q4); the odds ratio of SGA was OR = 3.02 (p = 0.019) for Q1 vs. Q2 quartile. The risk profile graph confirms the results. We found that excessive pre-pregnancy BMI (body mass index) affected the estimated SGA odds ratios. Early pregnancy maternal serum selenium status can be a risk marker of SGA newborns and more research is needed in larger groups.