Treatment Of Endometrial Cancer Patients Research Articles

RWD50 Progression-Free Survival after First-Line Treatment in Endometrial Cancer Patients: A Real-World Perspective from Brazil and Argentina

RWD50 Progression-Free Survival after First-Line Treatment in Endometrial Cancer Patients: A Real-World Perspective from Brazil and Argentina

Robotic surgery in endometrial cancer: first Polish experience.

In Poland, robotic surgery is nowadays perceived as a new method of surgical treatment in endometrial cancer patients. We aim to present the first Polish group of endometrial cancer patients treated using robotic surgery. The analysis was based on 79 patients with mean age of 59.72 ± 11.709 (range 27-83) years and endometrial cancer scheduled for surgical treatment. Mean BMI was 31.38 ± 8.78 (range 19.03-65.97)kg/m2. The data were collected based on a questionnaire consisting of 19 questions concerning the patient's perception of robotic surgery before the procedure. Patients with a family history of neoplastic diseases indicate precision of movements as the most important reason for choosing robotic surgery (p = 0.0035). Patients after surgery procedures in the past named shorter hospitalization as a major benefit (p = 0.0037). Patients who chose robotic surgery for financial reasons stressed the cosmetic effect as a priority (p = 0.0319). Shorter length of hospital stay, less blood loss, enlarged view, and good visualization were statistically significant reasons for choosing robotic surgery (p < 0.05). Women who consider work, good material status, and well-being as the most important aspects of their lives cited the cosmetic effect as a benefit of robotic surgery (p = 0.0029 vs. p = 0.0074 vs. p = 0.01745, respectively). In the follow-up after operations, no patients regretted choosing robotic surgery. Good visualization, precise movements, less blood loss, and cosmetic effects are the most frequent reasons for choosing robotic surgery. Even patients after other types of surgery in the past decided on robot-assisted radical hysterectomy because of the clear benefits of this approach.

Characteristics and outcomes of surgically staged multiple classifier endometrial cancer

ObjectiveThe growing adoption of molecular and genomic characterization is changing the current landscape of treatment of endometrial cancer patients. Using the surrogate molecular classification, endometrial cancer patients can be classified in four subgroups: POLE mutated (POLEmut), MMRd/MSI-H, p53 abnormal (p53abn), and no specific mutational profile (NSMP). However, some patients can harbor two or more molecular features (defined as multiple classifier). Since the rarity of this occurrence, evidence regarding multiple classifiers is still limited. Here, we described characteristics and outcomes of multiple classifiers. MethodsThis is a multi-institutional retrospective study. Data of consecutive patients having 2 or more molecular features were collected. Survival was assessed using the Kaplan-Meier and Cox proportional hazard methods. ResultsCharts of 72 multiple classifiers were reviewed. Median (range) follow-up was 9.8 (1.2, 37.5) months. Overall, 31 (43%) patients had POLEmut. Patients with POLEmut-MMRd/MSI-H, POLEmut-p53abn, and POLEmut-MMRd/MSI-H-p53abn were 6 (8.3%), 20 (27.8%), and 5 (6.9%), respectively. Among those 31 patients, no recurrence occurred within a median follow-up of 10.5 months (only seven (22.6%) patients had at least 2-year follow-up). The remaining 41 (56.9%) patients were diagnosed with tumors harboring both p53 and MMRd/MSI-H. Among them, four (9.8%) recurrences occurred at a median follow-up time of 8.9 months. Adjuvant therapy (other than vaginal brachytherapy) was administered in 5/31 (16%) and 25/41 (61%) patients with and without POLEmut, respectively (p < 0.001). ConclusionsMultiple classifiers endometrial cancer with POLEmut are characterized by good prognosis even in case of presence of MMRd/MSI-H and/or p53abn. Additional studies with long-term follow-up are needed.

The role of lymph node dissection in the surgical treatment of endometrial cancer patients (retrospective analysis).

Endometrial cancer in recent years has taken the lead among cancer processes of the female reproductive system. The feasibility of pelvic and para-aortic lymph node dissection in patients with endometrial cancer has always been a controversial issue. The aim of the presented paper is to evaluate the feasibility of pelvic and para-aortic lymph node dissection in patients with endometrial cancer, depending on the stage of the disease, postoperative complications, and patient survival, depending on the volume of surgical intervention. The study involved 285 patients with stages of I-IV endometrioid endometrial cancer of the Pre-graduate Department of Oncogynecology of the National Cancer Institute. The average age of patients was 55 ± 5.7years. In 74.5%, the disease was detected at stage I and uterine extirpation was performed with/without appendages. The duration of the operation varies depending on the volume of intervention-from 1h 30min ± 10min for panhysterectomy, up to 3h 20min ± 10min when performing para-aortic lymph node dissection. The average number of lymph nodes removed was-7 ± 1.1 pelvic and 12 ± 1.5 para-aortic. The basic principles of surgical treatment consist in individual choice of the scope of surgical intervention, performing adequate lymph node dissection, and preventing relapse and metastasis of the disease.

Characteristics and patterns of care of endometrial cancer before and during COVID-19 pandemic.

ObjectiveCoronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients.MethodsThis is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak.ResultsMedical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p<0.001). While, the prevalence of patients undergoing sentinel node mapping (with or without backup lymphadenectomy) has increased during the COVID-19 pandemic (46.7% in period 1 vs. 52.8% in period 2; p<0.001). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p<0.001). Adjuvant therapy use has increased during COVID-19 pandemic (p<0.001).ConclusionOur data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of EC patients. These findings highlight the need to implement healthcare services during the pandemic.

Fertility-sparing treatments decision in patients with endometrial cancer based on machine learning

Although many studies have been recently performed on fertility-sparing treatments in patients with endometrial cancer (EC) and endometrial atypical hyperplasia (EAH), most of the corresponding studies were retrospective and small sample research. However, it is essential to more thoroughly assess the necessity of hysterectomy in EC patients using current accumulated experience. With the development of machine learning (ML), it has been gradually integrated into oncologic research but seldom applied to predict the efficacy of hysterectomy due to an insufficient number of patients who did not undergo hysterectomy, leading to a learning imbalance. Thus, the commonly used machine learning models cannot provide satisfying performance. In this study, we aimed to develop ML models to predict whether hysterectomy is necessary for EC patients and help gynecologists determine the possibility of fertility-preserving treatment in EC patients. A clinical dataset of 1534 women with EC was analyzed. The Borderline-SMOTE algorithm was employed to solve imbalanced learning issues. Then, the Adaptive Boosting (AdaBoost) algorithm, which is less susceptible to overfitting than other machine learning algorithms, was used to build a high-performance ensemble classification model. The findings indicated that the method outperformed conventional machine learning models and provided a realistic strategy to make fertility-preserving treatment decisions. The proposed model provides a platform for physicians to precisely predict the efficacy of fertility-sparing therapy in EC patients, allows gynecologists to select the optimal treatment for a patient, and reduces resource waste and risks of overtreatment.

Examination of the Expression Level HOTAIR, MALAT1and H19 Genes and Single Nucleotide Polymorphisms rs920778, rs619586 and rs2839698 Respectively in the Same Genes, in Response to Treatment of Endometrial Cancer Patients

Examination of the Expression Level HOTAIR, MALAT1and H19 Genes and Single Nucleotide Polymorphisms rs920778, rs619586 and rs2839698 Respectively in the Same Genes, in Response to Treatment of Endometrial Cancer Patients

Tumor Promoting Effect of BMP Signaling in Endometrial Cancer.

The effects of bone morphogenetic proteins (BMPs), members of the transforming growth factor-β (TGF-β) family, in endometrial cancer (EC) have yet to be determined. In this study, we analyzed the TCGA and MSK-IMPACT datasets and investigated the effects of BMP2 and of TWSG1, a BMP antagonist, on Ishikawa EC cells. Frequent ACVR1 mutations and high mRNA expressions of BMP ligands and receptors were observed in EC patients of the TCGA and MSK-IMPACT datasets. Ishikawa cells secreted higher amounts of BMP2 compared with ovarian cancer cell lines. Exogenous BMP2 stimulation enhanced EC cell sphere formation via c-KIT induction. BMP2 also induced EMT of EC cells, and promoted migration by induction of SLUG. The BMP receptor kinase inhibitor LDN193189 augmented the growth inhibitory effects of carboplatin. Analyses of mRNAs of several BMP antagonists revealed that TWSG1 mRNA was abundantly expressed in Ishikawa cells. TWSG1 suppressed BMP7-induced, but not BMP2-induced, EC cell sphere formation and migration. Our results suggest that BMP signaling promotes EC tumorigenesis, and that TWSG1 antagonizes BMP7 in EC. BMP signaling inhibitors, in combination with chemotherapy, might be useful in the treatment of EC patients.

The Clinical Significance of DJ1 and L1CAM Serum Level Monitoring in Patients with Endometrial Cancer.

Circulating tumor markers are not routinely used in patients with endometrial cancer (EC). This pilot study evaluated the role of monitoring new biomarkers DJ1 and L1CAM, in correlation with CA125 and HE4, for the effects of anticancer treatment and preoperative management in EC patients. Serial serum levels of DJ1, L1CAM, CA125 and HE4 were collected in 65 enrolled patients. Serum DJ1, L1CAM, CA125 and HE4 levels were significantly higher at the time of diagnosis compared to those measured during follow-up (FU). In patients with recurrent disease, serum DJ1, CA125 and HE4 levels were significantly higher at the time of recurrence compared to levels in disease-free patients. Serum L1CAM levels were also higher in patients with recurrence but without reaching statistical significance. While DJ1 levels were not affected by any of the observed patient-related characteristics, L1CAM levels were significantly higher in patients with age ≥60 years who were overweight. At the time of EC diagnosis, DJ1 and L1CAM serum levels did not correlate with stage, histological type or risk of recurrence. This is a preliminary description of the potential of serial DJ1 and L1CAM serum level measurement for monitoring the effects of treatment in EC patients.

The long-noncoding RNA SOCS2-AS1 suppresses endometrial cancer progression by regulating AURKA degradation

Aberrant long-noncoding RNA (lncRNA) expression has been shown to be involved in the pathogenesis of endometrial cancer (EC). Herein, we report a novel tumor suppressor lncRNA SOCS2-AS1 in EC. Quantitative real-time PCR was performed to detect RNA expression. In situ hybridization and nuclear/cytoplasmic fractionation assays were used to detect the subcellular location. We found that SOCS2-AS1 was downregulated in EC tissues. Its reduced expression was correlated with advanced clinical stage and poor prognosis. Forced expression of SOCS2-AS1 suppressed EC cell proliferation and induced cell-cycle arrest and apoptosis. SOCS2-AS1-binding proteins were detected using RNA pull-down assay and mass spectrometry. Mechanistically, SOCS2-AS1 bound to Aurora kinase A (AURKA) and increased its degradation through the ubiquitin-proteasome pathway. In conclusion, SOCS2-AS1 may thus serve as a prognostic predictor and a biomarker for AURKA-inhibitor treatment in EC patients.

Short-term outcomes for patients with endometrial cancer who received robot-assisted modified radical hysterectomy: A retrospective observational study

Objective: Minimally invasive surgery is a standard treatment for endometrial cancer patients with uterine-confined disease. Robot-assisted surgery has been covered under public insurance since 2018 in Japan. The aim of the current study was to compare the short-term outcomes between robot-assisted modified radical hysterectomy (RAMRH) and total laparoscopic modified radical hysterectomy (TLMRH). Methods: A total of 190 patients with endometrial cancer who had undergone RAMRH or TLMRH were retrospectively reviewed. Short-term outcomes, including surgical time, estimated blood loss, complications, and hospital stay, were compared between the groups. Results: Among 190 patients, including 67 with RAMRH and 123 with TLMRH, the median (interquartile range [IQR]) surgical time was 247 (IQR: 221-313) min in RAMRH and 271 (IQR: 236-280) min in TLMRH. The estimated blood loss was less than 10 mL in most cases. There was 1 major vessel injury and 1 vescio-vaginal fistula in the RAMRH group. In contrast, there were 2 bladder injuries, 1 bowel injury, 2 obturator nerve injuries, 1 major vessel injury, and 2 pelvic abscesses in the TLMRH group. The median hospital stay was 10 (IQR: 10-10) days in RAMRH and 9 (IQR: 9-10) days in TLMRH. Conclusion: Robot-assisted procedures were not associated with poorer short-term outcomes than laparoscopy in patients with endometrial cancer.

COMBINED APPROACH TO SURGICAL TREATMENT OF ENDOMETRIAL CANCER IN PATIENTS WITH MORBID OBESITY

The purpose of the study was to evaluate a combined approach to surgical treatment of patients with morbid obesity. Material and methods . Between January 2017 and December 2018, 26 women with stage I endometrial cancer underwent laparoscopic gysterectomy in combination with panniculectomy. Results . No episodes of intraoperative hemodynamic instability, significant hypoxemia or hypercapnia were reported. The average blood loss was 236.4 ± 114.8 ml; surgery time: 264.2 ± 57.3 min; mass of the removed flap: 10.52 ± 6.5 kg; length of hospital stay: 11.2 ± 3.7 days. There was no delay in the start of adjuvant radiation therapy. Conclusion. Surgical treatment of endometrial cancer patients with morbid obesity presents significant technical challenges. The choice of surgical access in such cases may depend not on the stage and prevalence of the tumor, but on the constitutional characteristics of the patients. Sometimes surgeons can refuse to perform surgery for such patients and offer them an alternative treatment. Classical laparotomic access is associated with the maximum risk of perioperative complications. Laparoscopic techniques have technical limitations associated, for example, with the length of trocars and surgical instruments. Robotic surgery is considered generally safe, but due to its low availability, it is limited only to large clinical centers . The combined approach to surgical treatment of endometrial cancer patients with morbid obesity is the most effective surgical modality for these patients.

Effect of Metformin For Decreasing Proliferative Marker in Women with Endometrial Cancer: A Randomized Double-blind Placebo-Controlled Trial.

Objective:To compare the Ki-67 index of endometrial cancer cells before and after treatment between the metformin and placebo group in women with endometrial cancer (EC). Methods:This study was a randomized, double-blind, placebo-controlled trial conducting in non-diabetic women who diagnosed with endometrioid EC and had a schedule for elective surgical staging at Rajavithi Hospital between August 2018 and June 2019. Tissue specimens were obtained via endometrial curettage at the time of initial diagnosis (pre-treatment) and hysterectomy (post-treatment) to assess the value of the Ki-67 index by immunochemistry. Patients were randomly assigned into 2 groups: metformin and placebo group. Metformin 850 mg or placebo 1 tab were administered once daily for at least 7 days, starting on the first morning after recruitment until one day before surgery. Baseline characteristics (e.g., age, body mass index, co-morbidities) including surgical and pathological characteristics were recorded. The metabolic effect of metformin was also evaluated by a recording of fasting blood sugar, HbA1C and potential adverse events including nausea, vomiting, dizziness, and hypoglycemic symptom. Results:A total of 49 EC patients were included in this study. Twenty-five patients were assigned to the metformin group and 24 patients were assigned to the placebo group. Baseline demographic, surgical, and pathological characteristics between the 2 groups were similar. Metformin significantly changed the Ki-67 index relative to placebo, with a mean decrease of 23.3% (p=0.001) and a mean proportional decrease of 39.1% (p=0.006) before and after treatment. Additionally, no significant differences were detected in metabolic effects and adverse events between the metformin and the placebo groups. Conclusion:Short-term treatment with an oral metformin significantly reduced a proliferative marker Ki-67 index in women with endometrioid EC awaiting surgical staging. This study supports the biological effect of metformin in EC and potential applications in the adjuvant treatment in EC patients.

PO-1042 Toxicity results after Electronic Brachytherapy treatment in endometrial cancer patients

PO-1042 Toxicity results after Electronic Brachytherapy treatment in endometrial cancer patients

Vaginal hysterectomy with or without bilateral salpingo-oophorectomy may be an alternative treatment for endometrial cancer patients with medical co-morbidities precluding standard surgical procedures: a systematic review.

Vaginal hysterectomy with bilateral salpingo-oophorectomy may be an alternative strategy for patients with low-risk endometrial cancer and medical co-morbidities precluding laparoscopic or abdominal procedures. The current study evaluates the prevalence of co-existent ovarian malignancy in patients with endometrial cancer and the influence of bilateral salpingo-oophorectomy on survival outcomes in these patients. Medline and EMBASE were searched for studies published between January 1, 2000 and November 20, 2017 that investigated (1) the prevalence of co-existing ovarian malignancy (either metastases or primary synchronous ovarian cancer in women with endometrial cancer, and (2) the influence of bilateral salpingo-oophorectomy on recurrence and/or survival rates. Of the pre-menopausal and post-menopausal patients (n=6059), 373 were identified with metastases and 106 were identified with primary synchronous ovarian cancer. Of the post-menopausal patients (n=6016), 362 were identified with metastases and 44 were identified with primary synchronous ovarian cancer. Survival outcomes did not differ for pre-menopausal patients with endometrial cancer with and without bilateral salpingo-oophorectomy (5-year overall survival rates were 89-94.5% and 86-97.8%, respectively). Bilateral salpingo-oophorectomy during vaginal hysterectomy seems to have a limited impact on disease outcome in patients with endometrial cancer. These results support the view that vaginal hysterectomy alone or with bilateral salpingo-oophorectomy may be an option for patients with endometrial cancer who are not ideal surgical candidates.

Antitumor effects of metformin via indirect inhibition of protein phosphatase 2A in patients with endometrial cancer.

ObjectiveMetformin, an antidiabetic drug, inhibits the endometrial cancer cell growth in vivo by improving the insulin resistance; however, its mechanism of action is not completely understood. Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase associated with insulin resistance and type 2 diabetes, and its inhibition restores the insulin resistance. This study investigated the antitumor effect of metformin on endometrial cancer with a focus on PP2A.MethodsMetformin (1,500–2,250 mg/day) was preoperatively administered to patients with endometrial cancer for 4 to 6 weeks. Expression of the PP2A regulatory subunits, 4 (PPP2R4) and B (PP2A-B), was evaluated using real-time polymerase chain reaction (RT–PCR) and immunohistochemistry (IHC) using paired specimens obtained before and after metformin treatment. The effect of PPP2R4 inhibition with small interfering RNA was evaluated in the endometrial cancer cell lines HEC265 and HEC1B. P values of < .05 were considered statistically significant.ResultsPreoperative metformin treatment significantly reduced the expression of PP2A-B, as determined using IHC, and the mRNA expression of PPP2R4, as determined using RT–PCR, in the patients with endometrial cancer. However, metformin could not directly alter the PPP2R4 mRNA levels in the endometrial cancer cell lines in vitro. PPP2R4 knockdown reduced the proliferation and induced the apoptosis by activating caspases 3/7 in HEC265 and HEC1B cells.ConclusionsDownregulation of the PP2A-B subunit, including PPP2R4, is an important indirect target of metformin. Inhibition of PP2A may be an option for the treatment of endometrial cancer patients with insulin resistance.Trial registrationThis trial is registered with UMIN-CTR (number UMIN000004852).

Clinical importance of serum HE4 and MMP2 levels in endometrial cancer patients

IntroductionEndometrial cancer is the one of the most common cancers of the genital organ. HE4 and MMP2 are both proteins whose serum levels increase in endometrial cancer.AimTo explore the diagnostic potential of the serum levels of HE4 and MMP2 in patients with endometrial cancer and benign endometrial diseases. To assess the relationship between the serum levels of HE4 and MMP2 and the typical prognostic factors in patients with endometrial cancer.Materials and methodsIncluded in the study was a group of 112 patients presenting with bleeding abnormalities at the Pomeranian Medical University in years 2012–2016. Serum HE4 concentrations were measured using the Elecsys Electrochemiluminescence Immunoassay (ECLIA). MMP2 concentrations were quantified in the serum using multiplex immunoassays.ResultsWe observed statistically significant differences in mean serum levels of HE4 and MMP2 between the group of endometrial cancer patients and the group of patients with no changes in the endometrium (P=0.002/0.003). The diagnostic potential of HE4 and MMP2 in differentiation of high (International Federation of Gynecology and Obstetrics [FIGO] III and IV) vs low (FIGO I and II) clinical stage of tumor and prediction of cellular differentiation grade (G1 vs G3) on the basis of the analysis of the area under the curve is, respectively, 0.86 and 0.82 for HE4 and 0.82 and 0.74 for MMP2. The HE4 marker was significantly more specific than MMP2 in every study group and amounted to 93% vs 86% in all patients included in the analysis, 94% vs 84% in pre-menopausal patients and 84% vs 79% in post-menopausal patients.ConclusionHE4 and MMP2 are characterized by high specificity and may be useful as biomarkers in the diagnostics of endometrial cancer. When determined preoperatively, HE4 is correlated with the prognostic factors of endometrial cancer and may be helpful in the planning of individual treatment of endometrial cancer patients.

State of care in patients with endometrial cancer in Zaporizhzhia region since 2008 to 2015 year

Endometrial Cancer (EC) is a relevant problem both in Ukraine and in the world.Aim. Our goal was to analyze morbidity and survival rate of the EC patients in Zaporizhzhia region from 2008 to 2015 and to study the state of giving help to the mentioned category of patients.Materials and methods. During the study it was revealed that from 2008 to 2015 in Zaporozhye 2719 patients with EC where registered. Total survival rate of this category of patients made 68.8 % in 5 years period.During the research it was found that we can relate the stage of the disease, morphological type of the tumor and age of the patient to the factors which impact the total survival rate of the patients with EC. Thus, the best survival rate is determined among women with the first stage of neoplastic process, it made 81.0 %, also the highest indexes where determined in age group from 45 to 65, which made 76.8 %. And total survival rate of adenocarcinoma EC made 72.6 % (p < 0,05).Results. During the ranking of the conducted treatment effectiveness the next sequence can be mentioned: 1 place - surgery without radiotherapy and chemotherapy, the overall 5-year survival rate for patients who received this type of treatment was 86.9 % (p <0.05); second place - combined treatment (surgery + radiotherapy), the overall 5-year survival rate for these women was 85.2 % (p < 0.05); third place - complex treatment (surgery + radiotherapy + chemotherapy), the overall 5-year survival rate for patients in this case amounted to 65.0 % (p < 0.05); fourth place - patients who received integrated treatment (radiotherapy + chemotherapy), the overall 5-year survival rate – 57.3 % (p < 0.05); fifth place - surgery + chemotherapy, the overall 5-year survival rate – 55.0 % (p < 0.05). The worst outcome of treatment was seen in women with ER who received radiotherapy in mono and palliative chemotherapy: overall 5-year survival rate was 47.4% (p < 0.05) and 42.7 % (p < 0.05), respectively. It is important to understand that one of the reasons for such a high efficiency of surgical mono treatment is its use in patients with initial stages of OM.Conclusion. The given research allowed us to set goals, completing which is necessary for improving aid for patients with EC in Zaporizhzhia. Thus, we have to establish the clear surgical staging of EC, the detailed staging and treatment data entry into cancer-register. We need to improve the quality and control of regular medical examination by gynecologist, which will allow to diagnose EC on the early stages. Treatment of EC patients must be performed in specialized medical centers, which will improve both immediate and further results of this pathology treatment.

DNA methylation as mechanism of apoptotic resistance development in endometrial cancer patients.

DNA methylation is a significant epigenetic modification which plays a key role in regulation of gene expression and influences functional changes in endometrial tissue. Aberrant DNA methylation changes result in deregulation of important apoptotic proteins during endometrial carcinogenesis and apoptosis resistance development. Evading apoptosis is still a major problem in the successful treatment of endometrial cancer patients. The aim of our study was to examine the promoter DNA methylation changes in 22 apoptosis-associated genes in endometrioid endometrial cancer patients, precancerous lesions and healthy tissue from various normal menstrual cycle phases using a unique pre-designed methylation platform. We observed as the first a significant difference in promoter DNA methylation status in genes: BCL2L11 (p < 0.001), CIDEB (p < 0.03) and GADD45A (p < 0.05) during endometrial carcinogenesis and BIK gene (p < 0.03) in different phases of normal menstrual cycle. The results of our study indicate that deregulation of mitochondrial apoptotic pathway can considerably contributes to the apoptosis resistance development and may be helpful in identifying of new potent biomarkers in endometrial cancer.

DNA Methylation Machinery in the Endometrium and Endometrial Cancer.

During the normal menstrual cycle, endometrial tissue undergoes many biochemical and morphological changes which are under the control of steroid hormone levels. DNA methylation plays a key role in gene expression regulation and influences functional changes in endometrial tissue. Eliminating senescent cells from the functional layer of the endometrium is mediated by apoptotic cell death, which helps maintain cellular homeostasis. Aberrant DNA methylation changes result in deregulation of important apoptotic proteins during endometrial carcinogenesis and thus apoptosis resistance development. Evading apoptosis is still a major problem in the successful treatment of endometrial cancer patients with advanced disease. Despite intensive study of the cancer epigenome, there is missing information about disrupted apoptotic gene regulation in DNA methylation levels. Therefore, it is necessary to spread our knowledge in the field of epigenetics to help us differentiate normal and cancer tissues and detect the early stages of cancer disease.