Trends in Systemic Inflammatory Reaction (SIR) during Paclitaxel and Carboplatin Chemotherapy in Women Suffering from Epithelial Ovarian Cancer.

BACKGROUND: Epithelial ovarian cancer (EOC) is the most fatal gynaecological malignancy treated with cytoreductive surgery followed by adjuvant taxane-platinum-based chemotherapy. It has been shown that the pretreatment systemic inflammatory reaction (SIR) in women with OC can be evaluated using the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR) and systemic inflammatory index (SII), depending on the stage of disease, and has prognostic value for overall survival. The aim of this study was to evaluate the changes in NLR, LMR, PLR and SII during chemotherapy. METHODS: A total of 107 women with EOC (23 with type I and 84 with type II tumours) were included in a retrospective single-centre analysis. The Kologomorov-Smirnoff, Kruskal-Wallis or Friedman analysis of variance tests were used for data analysis, and a p value of 0.05 was considered statistically significant. RESULTS: A significant decrease in NLR, PLR and SII but not LMR was observed during adjuvant treatment. Pretreatment NLR, PLR and SII were dependent on disease stage and tumour grade; however, this association was lost during therapy. Additionally, strong and positive mutual correlations between NLR, LMR, PLR and SII were sustained during the whole course of chemotherapy. CONCLUSIONS: During first-line adjuvant chemotherapy in women with EOC, a decrease in SIR is confirmed.

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.

A patient with advanced breast cancer and hyperthyroidism associated with struma ovarii.

Not required for Clical Vignettes.

Metastases and Recurrence Risk Factors in Endometrial Cancer-The Role of Selected Molecular Changes, Hormonal Factors, Diagnostic Methods and Surgery Procedures.

The presence of metastatic endometrial cancer (EC) is a key problem in treatment failure associated with reduced overall survival rates. The most common metastatic location is the pelvic lymph nodes, and the least common is the brain. The presence of metastasis depends on many factors, including the molecular profile of cancer (according to the TCGA-Genome Atlas), the activity of certain hormones (estrogen, prolactin), and pro-inflammatory adipocytokines. Additionally, an altered expression of microRNAs affecting the regulation of numerous genes is also related to the spread of cancer. This paper also discusses the value of imaging methods in detecting metastases; the primary role is attributed to the standard transvaginal USG with the tumor-free distance (uTFD) option. The influence of diagnostic and therapeutic methods on EC spread is also described. Hysteroscopy, according to the analysis discussed above, may increase the risk of metastases through a fluid medium, mainly performed in advanced stages of EC. According to another analysis, laparoscopic hysterectomy performed with particular attention to avoiding risky procedures (trocar flushing, tissue traumatization, preserving a margin of normal tissue) was not found to increase the risk of EC dissemination.

Identification of PDGFRα+ cells in uterine fibroids - link between angiogenesis and uterine telocytes.

Introduction: Telocytes (TCs), also called interstitial Cajal-like cells (ICLC), CD34+ cells or PDGFRα+ cells (platelet-derived growth factor receptor α positive cells), a new type of cell of mesenchymal origin, were described over one decade ago. The unique nature of these cells still deserves attention from the scientific community. Telocytes make homo- and heterocellular contact with myocytes, immunocytes and nerves, have their own immunohistochemical and secretome profiles and thus might regulate local regenerative processes including angiogenesis and fibrosis. The aim of our study was to observe the missing link between angiogenesis and telocytes in leiomyoma, the most common benign tumors affecting women of reproductive age. Material and methods: We observed uterine tissue samples from leiomyoma, adjacent myometrium and unchanged tissue from patients with leiomyoma and control subjects using routine histology, histochemistry, immunofluorescence (CD117, CD31, CD34, PDGFRα, tryptase, sFlt-1) and image analysis methods. Results: The decline of the telocyte density in the foci of fibroids correlated with poor vascularization inside the leiomyoma. Moreover, the expression of sFlt-1 (anti-angiogenic-related factor) significantly increased inside a fibroid. In leiomyoma the decrease of telocyte and blood micro-vessel density was accompanied by prevalence of collagen deposits, unlike the unchanged myometrium. Conclusions: Our results demonstrate TCs in human uterine fibroids and highlight their possible involvement in the pathogenesis of myometrial pathology in the context of angiogenesis.

Oviductal Oxygen Homeostasis in Patients with Uterine Myoma: Correlation between Hypoxia and Telocytes.

Oxygen balance is crucial for angiogenesis, immunity, and tissue repair. The human oviduct is essential for reproductive function, and any imbalance in homeostasis leads to fertility disturbances and might be a reason for ectopic pregnancy development. Uterine myoma is a widespread benign tumour, which is often accompanied by infertility. Telocytes have been discussed in the contexts of motility, fibrosis development, and angiogenesis. We observed the oviducts from patients with and without uterine myoma, comparing the expression of HIF-1, HO, VEGF and its receptor, NOS, oestrogen, and progesterone receptors by immunolabeling. The myometrial and oviductal telocytes were also compared in both groups. Biochemical analyses were conducted for FSH, LH, AMH, sFlt, oestrogen, and progesterone in blood samples. Patients with uterine myoma have different expressions of sex steroid receptors and an increased number of telocytes. The decreasing VEFG expression was compensated by the rise in the HIF-1 and NOS expression. Blood biochemical analyses revealed a higher progesterone level and lower AMH in patients with uterine myoma. No differences in sFlt, FSH, and LF were observed. Uterine myoma impacts oviduct oxygen homeostasis and might cause fertility disturbances (uterine and oviductal infertility factors).

Endometrial Cancer Management in Young Women.

Endometrial cancer (EC) rarely develops in young women. Most cases are associated with known risk factors: BMI > 30, history of Polycystic Ovary Syndrome (PCOs), and race differentiation. The molecular EC classification based on The Cancer Genome Atlas Research Network divides these heterogeneous cancers into four types: Polymerase Epsilon Mutation (POLE), Microsatellite Instability (MSI), Copy Number Low (CNL), and Copy Number High (CNH). This division was introduced to allow for early assessment of neoplastic changes and clinical management, including targeted therapies. The basic technique for imaging endometrium changes is transvaginal sonography. Hysteroscopy is the standard for obtaining endometrial material for histological evaluation. The MRI result permits assessment of the extent of EC cancer infiltration. In young women who want to preserve fertility, apart from surgery, conservative management is often implemented after strict selection based on clinical and pathological data. This pharmacological treatment involves the administration of progestogens MPA (medroxyprogesterone acetate) and MA (megestrol acetate). The use of metformin may increase the effectiveness of such treatment. An alternative option is to apply progestogens locally­via the levonorgestrel-releasing intrauterine device. In addition to pharmacological treatment, hysteroscopic resection may be used­part of the uterine muscle adjacent to the pathologically changed endometrium may also undergo resection. An alternative is the administration of estrogen receptor modulators (e.g., SERMs) or aromatase inhibitors, or GnRH agonists.

Ultrasound differentiation between benign versus malignant adnexal masses in pregnant patients.

OBJECTIVES: The aim of this study was to assess the performance of the International Ovarian Tumor Analysis (IOTA) group ultrasound Simple Rules method in differentiating between benign and malignant ovarian tumors in pregnant patients. MATERIAL AND METHODS: A prospective observational study that involved pregnant patients referred to our center due to suspicions of ovarian masses between January 2015 and December 2017 was performed. The Simple Rules performance was evaluated against the histopathological results. Each of the 10 sonographic Simple Rules were computed by logistic regression to demonstrate their odds ratios in predicting malignancy. RESULTS: Ultrasound were conducted in 153 subjects, and 61 of those patients underwent surgery. By assigning masses presenting inconclusive picture as probably malignant, the Simple Rules method showed sensitivity of 91.67% and specificity of 69.39%. After exclusion of masses with inconclusive findings, the method showed sensitivity of 87.5% and specificity of 94.44%. The Simple Rules risk estimation method for the 1% risk cutoff showed sensitivity of 100% and specificity of 51.02%. For the 3% cutoff, sensitivity was 91.67% and specificity was 53.06%. And for 30 % cutoff, sensitivity was 91.67% and specificity 73.47 %. The logistic regression model showed that the M-rules increased the risk of malignancy while the B-rules decreased the risk. CONCLUSIONS: Most ovarian masses in pregnant patients may be correctly categorized as benign or malignant using Simple Rules. This protocol may facilitate the management of pregnant patients presenting with adnexal masses.

Oviductal Telocytes in Patients with Uterine Myoma.

Tubal factor infertility occurs in 30-35% of infertile pairs and may be caused by impaired muscular contractility and ciliary beating as well as immunological imbalance and chronic inflammation. Newly discovered telocytes (TCs) have a wide palette of features, which play a role in oviduct physiology. We have observed tissue samples from human fallopian tubes in patients with and without uterine myoma by immunolabelling. According to the immunohistochemical co-expression of markers, it has been determined that TCs are engaged in a wide range of physiological processes, including local innervation, sensitivity to hypoxia, regulation of calcium, and sex steroid hormones balances. Due to the proximity of NOS- and ChAT-positive nerve fibers and the expression of ion channels markers, tubal TCs might be considered conductor cells. Additionally, their integration in contractions and cilia physiology in the context of fertility has been revealed. We have observed the difference in telocytes expression in the human oviduct between groups of patients and attempted to describe this population of cells specifically in the case of infertility development, a clinically relevant avenue for further studies.

Role of Systemic Inflammatory Reaction in Female Genital Organ Malignancies - State of the Art.

Systemic inflammatory reaction (SIR) is an unfavorable prognostic factor in many malignancies and has a role in all stages of the neoplastic process: initiation, promotion, and disease progression. Analysis of SIR can be performed by assessing indicators (eg, lymphocyte-to-neutrophil, platelet-to-lymphocyte, and monocyte-to-neutrophil ratios) and products of neutrophils and lymphocytes (ie, the systemic immune-inflammation index), or by examining the relationship between levels of C-reactive protein and albumin (based on the Glasgow Prognostic Score, modified Glasgow Prognostic Score, and C-reactive protein-to-albumin ratio). Risk stratification is essential in the clinical management of cancer; hence, the evaluation of these factors has potential applications in the clinical management of patients with cancer and in the development of new therapeutic targets. This review summarizes the current knowledge on SIR indicators and presents their clinical utility in malignancies of the female genital organs.

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.

COLPOSCOPY 2020 - COLPOSCOPY PROTOCOLS: A Summary of the Clinical Experts Consensus Guidelines of the Polish Society of Colposcopy and Cervical Pathophysiology and the Polish Society of Gynaecologists and Obstetricians.

The Polish Society of Colposcopy and Cervical Pathophysiology and the Polish Society of Gynecologists and Obstetricians provide comprehensive guidelines for colposcopy practice in secondary cervical cancer prevention in Poland. This part of the guidelines, developed by the clinical experts of the Working Group No. 1 (WG1), concerns the colposcopy protocols with the main aim of algorithmizing the procedure, together with all procedure-related processes. The detailed analysis of strong scientific evidence and an extensive literature review of current international colposcopic recommendations were carried out, with also a broad investigation of recently ongoing dynamic changes in national health systems. The attention to colposcopic limitations also occurring in Polish conditions was kept. The overriding goal was the recommended obligatory minimal colposcopy approach introduction. To enhance the standard of colposcopy, adjustment of a precolposcopic assessment, a performance technique, types of used biopsies, as well as the procedure documentation was made. Elements of the risk-based stratification for the increased risk of developing cervical cancer was also included if it was applicable for that part of the guidelines. Comprehensive colposcopy guidelines are a step towards the ongoing era of a precision medicine in cervical cancer prevention in Poland.

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.

Early fetal cardiac scan as an element of the sonographic first-trimester screening.

Early fetal cardiac scan (EFCS) is becoming an increasingly common element of the first trimester ultrasound screening carried out at 11-14 gestational weeks. It offers the first possibility to detect congenital heart defects (CHD) or, in ambiguous cases, to identify those pregnancies where a more detailed cardiac scan would be required later in pregnancy. The size of the fetal heart at the end of the first trimester and the associated relatively low image resolution make it impossible to capture all cardiac data to inform the ultimate picture. However, even at this stage, cues of anatomical and functional abnormalities can be picked up, which suggest not only a CHD, but also a likelihood of cardiovascular symptoms typical of genetic disorders. EFCS should focus on cardiac position, atrioventricular (AV) connections, AV valve function, initial assessment of ventriculo-arterial (VA) connections and the presence of red flag signs in the three vessel and trachea view (3VTV). Proper use of color Doppler mapping makes it possible to overcome the low resolution of B-mode to a certain extent. Here we present our long-term experience in EFCS.

[Vitamin D in normal and pathologically changed endometrium].

More and more evidence from research confirms the significance of vitamin D (VD) in the development of endometrial pathologies. Apart from the well known role of VD in regulation of calcium levels, VD acts as modulator to many genes involved in cell growth, immunological functions and protein synthesis. The newest research shows that VD acts multidirectionally and its common deficiency has a causal link to the pathogenesis of many gynecological and cancerous conditions. It is postulated that VD affects the endometrium via various mechanisms. The discovery that most tissues have VD receptors was ground-breaking in understanding its role in various medical conditions, including the neoplasmal development mechanism, but the degree, to which the VD metabolism in the eutopic endometrium during pathological conditions is impaired, has not yet been explained.

Coexistence of tooth agenesis and ovarian cancer - a systematic literature review.

OBJECTIVES: Dental agenesis - a congenital lack of teeth - is one of the most frequently diagnosed developmental defects of dentition. Genetics is a crucial factor in the etiology of this disorder. Missing teeth can be caused by mutation in genes including MSX1, PAX9, AXIN2, and EDARADD. As is also true for ovarian cancer, over 20% of cases are associated with hereditary factors. Mutations in the BRCA1 and BRCA2 genes are said to be the most frequent of these. The aim of this study was to provide a systematic review of the literature on the coexistence of ovarian cancer and tooth agenesis. MATERIAL AND METHODS: Publications were searched for in the online databases PubMed, SCOPUS, and Wiley Online Library. Current and archival issues of the Journal of Stomatology and Dental and Medical Problems were also searched. The key words used to find relevant publications were: ovarian cancer, hypodontia, and tooth agenesis, in various combinations. RESULTS: Three publications were qualified to this review. Two of these compared the incidence of hypodontia in women with ovarian cancer and in healthy women, and the other was aimed at locating the gene responsible for the coexistence of ovarian cancer and tooth agenesis. As shown by these studies, women with ovarian cancer are (depending on the study) 3.3 or 8.1 times more likely to have hypodontia than healthy women. However, no specific gene was found that might be responsible for the coexistence of ovarian cancer and tooth agenesis.

Immunoexpression of DNA fragmentation factor 40, DNA fragmentation factor 45, and B-cell lymphoma 2 protein in normal human endometrium and uterine myometrium depends on menstrual cycle phase and menopausal status.

INTRODUCTION: DNA fragmentation factors 40 and 45 (DFF40 and DFF45) are final executors of apoptosis, and B-cell lymphoma 2 (Bcl-2) is a well-recognized apoptosis inhibitor. We aimed to evaluate DFF40, DFF45 and Bcl-2 immunoexpression in the normal human endometrium with respect to the glandular and stromal layer and in uterine myometrium. MATERIAL AND METHODS: DFF40, DFF45, and Bcl-2 expression was assessed via immunohistochemistry in the endometrium and myometrium collected postmenopausally and premenopausally during the proliferative and secretory phases of the menstrual cycle. RESULTS: Compared to the myometrium and stroma, endometrial glands showed the highest DFF40 and DFF45 expression in pre- and postmenopausal specimens. DFF45, but not DFF40, glandular expression dependent on menstrual cycle phase and DFF40 and DFF45 scoring was significantly lower in postmenopausal specimens. Significantly higher Bcl-2 expression was observed in proliferative glandular endometrium compared to secretory and postmenopausal specimens. No cycle- or menopause-dependent changes were reported for stromal or myometrial DFF40, DFF45 or Bcl-2 expression. DFF40, DFF45 and Bcl-2 expression was independent of age, age at menarche and menopause, BMI, menstrual cycle and menses lengths, parity and gravidity. CONCLUSIONS: The study provides important evidence regarding menstrual cycle-dependent changes in the expression of DFF40, DFF45 and Bcl-2 in the normal human endometrium, especially in the glandular layer, and shows that their levels are stable in the normal uterine myometrium.

Occult uterine leiomyosarcoma in women undergoing abdominal and minimally invasive surgeries for myomas.

OBJECTIVES: To estimate (i) the incidence of occult uterine leiomyosarcoma (LMS) in patients operated on for presumedmyomas, and (ii) the proportion of occult LMS to preoperatively diagnosed LMS in a tertiary center. MATERIAL AND METHODS: An Institutional Review Board-approved retrospective cohort study was performed. The electronicdatabase of 30,476 patients was searched for women who had undergone surgery due to presumed myomas (N = 2675) as well as those with uterine LMS recognized via histology (N = 10) between January 2010 and December 2016. RESULTS: Six of the 2675 treated women had occult LMS (incidence 1:446; 0.002; CI 0.0-0.013), and one underwent power morcellation (incidence 1:951; 0.001; CI 0.0-0.006). Parallel searching revealed that 6 of the 10 cases (60%) with uterine LMS recognized via histology were diagnosed postoperatively, whereas 4 of the 10 (40%) were diagnosed preoperatively. The incidence of LMS morcellation during laparoscopy was 1:951 and, when all MIS cases were included, 1:1178. The patient who underwent LMS morcellation was operated in the general surgery ward 5 years after laparoscopy (omental recurrence). CONCLUSIONS: These results are similar to the first and recent conservative FDA estimations, but two-times lower for procedures with laparoscopic morcellation and all MIS procedures than for abdominal. Because above half of LMS may be recognized after surgery, the risk of occult LMS and the delay of targeted surgical treatment should be included in all informed consent forms for conservative management of presumed myomas without histology.

Non-endometrioid and high-grade endometrioid endometrial cancers show DNA fragmentation factor 40 (DFF40) and B-cell lymphoma 2 protein (BCL2) underexpression, which predicts disease-free and overall survival, but not DNA fragmentation factor 45 (DFF45) underexpression.

BACKGROUND: The expression of DNA fragmentation factor 45 (DFF45) and B-cell lymphoma 2 (BCL2) in glands of the normal human endometrium is related to phases of the menstrual cycle and decreases after menopause, whereas the expression of DNA fragmentation factor 40 (DFF40) is stable. Moreover, DF45, BCL2 and DFF40 underexpression has been reported in numerous malignancies, including uterine leiomyosarcomas. In this study, we aimed to investigate DFF45, BCL2 and DFF40 expression in endometrioid and non-endometrioid types of endometrial cancers (ECs). We also evaluated the correlations between DFF45, BCL2 and DFF40 expression levels and clinicopathological parameters and determined the value of these three proteins as prognostic markers of disease-free survival (DFS) and overall survival (OS). METHODS: Immunohistochemistry was performed to evaluate DFF45, BCL2 and DFF40 expression in 342 cases of ECs. Student's t-test, the Mann-Whitney U-test, and the chi-squared test were used for the statistical analyses as appropriate. The Cox-Mantel test, Cox's proportional hazard model, and relative risk analyses were used to evaluate associations between DFF40, DFF45, and BCL2 expression and clinicopathological characteristics. RESULTS: DFF40 and BCL2, but not DFF45, were significantly underexpressed in non-endometrioid and high-grade endometrioid ECs compared with low- and moderate-grade endometrioid ECs. Women with DFF40- and BCL2-negative tumors had higher risks of disease recurrence, lymph node involvement, lympho-vascular space infiltration, and deep myometrial invasion compared with women with DFF40- and BCL2-positive tumors. Additionally, women with DFF40- and BCL2-negative tumors had significantly lower OS and DFS than women with DFF40- and BCL2-positive tumors. A multivariable analysis of the model, including the clinicopathological characteristics and immunohistochemical results, showed that negative BCL2 expression, lymph node involvement, and high-stage and high-grade disease were independent predictors of OS, whereas negative BCL2 expression, lymph node involvement, and high-stage disease were independent predictors of DFS. CONCLUSIONS: Compared with low- and moderate-grade endometrioid ECs, non-endometrioid and high-grade endometrioid ECs showed significant DFF40 and BCL2 underexpression. The absence of DFF40 and BCL2 expression negatively affects DFS and OS. Further prospective studies are warranted to assess the potential utility of DFF40 and BCL2 as targets in the diagnosis or treatment of ECs.