Endometrial carcinoma (EC) is the most common cancer of the female reproductive system. In the United States, EC was the sixth-cause of cancer-related death in 2018, accounting for 11,350 deaths. The disease affects an estimated 1 out of every 37 and 49 women respectively during their lifetime in the United States and Australia [1,2]. The outlook for 5-year survival after treatment ranges from 74% to 91% [3,4]. EC has been historically classified into estrogen dependent (type I) and estrogenindependent (type II) cancers [4]. Type II tumors are less common, more clinically aggressive, and may have serous, clear cell or undifferentiated histology. In contrast, type I tumors present in 70%-80% of cases, with endometrioid histology and a more favorable outcome. The updated classification of EC identifies four molecular subtypes according to The Cancer Genomic Atlas (TCGA): "POLE-mutated (ultramutated), microsatellite unstable (hypermutated), copy number low (endometrioid), and copy number high (serous-like)" [1]. The POLE-ultramutated subgroup holds great promise for the outlook of EC patients. The tumors have a more favorable outcome, and are usually noted to be of endometrioid type and associated with lymphoid infiltrates [5]. The POLE gene encodes the catalytic subunit of DNA polymerase epsilon, which synthesizes the leading strand of replicating DNA. The epsilon polymerase recognizes and removes mispaired nucleotides using exonuclease activity. This proofreading capacity of epsilon enables high fidelity DNA replication [6]. Mutations can occur in the exonuclease domain of the polymerase,

Background: Loss of mismatch repair (MMR) occurs frequently in endometrial carcinoma (EC) and is an important prognostic marker. However, the frequency of MMR deficiency (D-MMR) in EC remains inconclusive. This systematic review and meta-analysis addressed this inconsistency and evaluated related clinicopathology. Methods: Electronic databases were searched for articles: PubMed, Science Direct, Web of Science, EMBASE, and the Wiley Online Library. Data were extracted from 25 EC studies of D-MMR to generate a clinical dataset of 7,459 patients. A random-effects model produced pooled estimates of D-MMR EC frequency with 95% confidence interval (CI) for meta-analysis. Results: The overall pooled proportion of D-MMR was 24.477% (95% CI, 21.022 to 28.106) in EC. The Lynch syndrome subgroup had 22.907% pooled D-MMR (95% CI, 14.852 to 32.116). D-MMR was highest in type I EC (25.810) (95% CI, 22.503 to 29.261) compared to type II (13.736) (95% CI, 8.392 to 20.144). Pooled D-MMR was highest at EC stage and grades I-II (79.430% and 65.718%, respectively) and lowest in stages III-IV and grade III (20.168% and 21.529%). The pooled odd ratios comparing D-MMR to proficient MMR favored low-stage EC disease (1.565; 0.894 to 2.740), lymphovascular invasion (1.765; 1.293 to 2.409), and myometrial invasion > 50% (1.271; 0.871 to 1.853). Conclusions: Almost one-quarter of EC patients present with D-MMR tumors. The majority has less aggressive endometrioid histology. D-MMR presents at lower tumor stages compared to MMR-proficient cases in EC. However other metastatic parameters are comparatively higher in the D-MMR disease setting.

ObjectiveInvestigate PTEN gene expression and tumor aggressiveness in endometrial carcinoma specimens from patients living in either areas of depleted uranium [DU] pollution or unpolluted regions to determine any evidence for the effect of war pollution on the rising trends of cancer incidence in Iraq.ResultsTumor PTEN gene expression was significantly increased in patients living in the areas of high risk DU exposure, in comparison to patient tumors from low risk areas [P = 0.001]. The age distribution between the potentially DU exposed (55.09 ± 1.24) and unexposed subjects 56.38 ± 1.18) was not significant [P = 0.45]. Endometrial carcinoma aggressiveness was equivalent in both subject groups, with no significant differences in either tumour grade and [P = 0.286] stage distribution [P = 0.98]. Finally, there were no significant differences between the potentially exposed and unexposed subjects with regard to cervical [P = 0.532] or to ovarian involvement [P = 0.518]. The results linked environmental war pollutants [DU] to alterations in PTEN gene expression in endometrial carcinoma. Furthermore, this finding may explain the overall increasing cancer trends observed in Iraq. Strategies should be considered for the therapeutic targeting of cancers with elevated PTEN gene expression to improve patient outlook.

Background Endometrial carcinoma (EC) is classified into four distinct molecular subgroups. Patients with polymerase epsilon exonuclease domain mutated (POLE-EDM) tumors have the best prognosis of all. This meta-analysis consolidated the clinicopathology variations reported in the POLE-mutant subtype and survival parameters in patients with EC. Methods The following internet data bases were searched: PubMed, Web of science, Embase and Scimage directory. Data was extracted from eligible studies including sample size, number of positive POLE-mutant cases, EDM sequencing information, clinicopathologic, and survival data. Meta-analysis and a random-effects model produced pooled estimates of POLE prognostic parameters using 95% confidence intervals (CI), hazard ratios (HR), and odds ratios (OR). Results The meta-analysis included 11 cohort studies comprising 5508 EC patients (442 POLE EDM tumors). Patients with POLE mutant EC were associated with improved disease specific survival (HR = 0.408, 95% CI: 0.306 to 0.543) and progression-free survival (HR = 0.231, 95% CI: 0.117 to 0.456). POLE-mutated tumors were mostly endometrioid histology (84.480%; 95% CI: 77.237 to 90.548), although not significantly more than wild type tumors (OR = 1.386; p = 0.073). The POLE mutant tumors significantly present (p<0.001) at Federation of International of Gynecologists and Obstetricians (FIGO) lower stages I-II (OR = 2.955, p<0.001) and highest grade III (OR = 1.717, P = 0.003). The tumors are significantly associated with invasion less than half (<50%) of the myometrium (OR = 1.765, p = 0.001), but not deeply invasive EC (MI>50%, OR = 0.83, p = 0.34). POLE mutations significantly protected against lymph node metastases (OR = 0.202, p = 0.001), and have no clear association with lymph-vascular space invasion (OR = 0.967, 95% 0.713–1.310, p = 0.826). The tumors are predominantly of low ESMO risk stratification distribution (40.356%; 95% CI: 27.577 to 53.838). Conclusions POLE mutations serve as an important biomarker of favorable prognosis in EC. The tumors are characteristically high grade, early stage, and remain localized in the endometrium with reduced likelihood of lymph node metastasis for improved survival prospects and the lowest risk classification. These findings have implications for medical management of EC.

Preeclampsia (PE) is a major obstetric syndrome and represents a pregnancy hypertensive disease affecting about 2–8% of pregnancies. Typically, it occurs after 20 weeks of pregnancy, being classified as early or late in accordance with the gestational age at diagnosis or delivery. An imbalance between angiogenic and antiangiogenic factors has an important role in the pathophysiology of PE. It was hypothesized that the dysfunctional endothelium contributes to the pathogenesis of PE. A change in the production of Vascular endothelial growth factor (VEGR), a biomarker of endothelial dysfunction, is associated with this disease, whether presenting an increase, decrease, or being at a normal level. This study examined the associations between VEGF and preeclampsia and the importance of this VEGF as a predictor of its severity. This case-control study included 50 patients with preeclampsia and 50 normotensive pregnant women in the control group. Venous blood was aspirated from each patient, and VEGF levels were measured from sera. The mean VEGF for patients with mild PE was 29.410±18.976 pg/ml, for those with severe PE it was 36.188±36.98 pg/ml, and for normotensive women it was 92.104±154.715 pg/ml. There were significant differences in VEGF levels between the studied groups (P=0.024). This study showed that serum VEGF levels were significantly reduced in patients with preeclampsia compared with normotensive pregnant women, suggesting marked endothelial dysfunction. This led to widespread vasoconstriction and, in turn, caused hypertension and proteinuria.