Integrating proteomics and explainable artificial intelligence: a comprehensive analysis of protein biomarkers for endometrial cancer diagnosis and prognosis.

Endometrial cancer, which is the most common gynaecological cancer in women after breast, colorectal and lung cancer, can be diagnosed at an early stage. The first aim of this study is to classify age, tumor grade, myometrial invasion and tumor size, which play an important role in the diagnosis and prognosis of endometrial cancer, with machine learning methods combined with explainable artificial intelligence. 20 endometrial cancer patients proteomic data obtained from tumor biopsies taken from different regions of EC tissue were used. The data obtained were then classified according to age, tumor size, tumor grade and myometrial invasion. Then, by using three different machine learning methods, explainable artificial intelligence was applied to the model that best classifies these groups and possible protein biomarkers that can be used in endometrial prognosis were evaluated. The optimal model for age classification was XGBoost with AUC (98.8%), for tumor grade classification was XGBoost with AUC (98.6%), for myometrial invasion classification was LightGBM with AUC (95.1%), and finally for tumor size classification was XGBoost with AUC (94.8%). By combining the optimal models and the SHAP approach, possible protein biomarkers and their expressions were obtained for classification. Finally, EWRS1 protein was found to be common in three groups (age, myometrial invasion, tumor size). This article's findings indicate that models have been developed that can accurately classify factors including age, tumor grade, and myometrial invasion all of which are critical for determining the prognosis of endometrial cancer as well as potential protein biomarkers associated with these factors. Furthermore, we were able to provide an analysis of how the quantities of the proteins suggested as biomarkers varied throughout the classes by combining the SHAP values with these ideal models.

Intensity-modulated vaginal brachytherapy applicator and single- and multi-channel applicators in vaginal cuff brachytherapy.

Purpose: To compare the dosimetric performance of vaginal intensity-modulated brachytherapy (IM-BRT) applicator and single- (SC-BRT) and multi-channel brachytherapy (MC-BRT) applicators for vaginal cuff brachytherapy (VC-BRT). Material and methods: Fifteen patients with uterine-confined endometrium cancer who received adjuvant VC-BRT were included in this study. IM-BRT, SC-BRT, and MC-BRT treatment plans were created for two different clinical target volume (CTV) definitions: 1. Standard CTV, called CTVs; and 2. Virtually defined CTV, called CTVv, with asymmetrical tumor extension > 5 mm in thickness. Plan comparison was performed using dose-volume histogram (DVH) and treatment planning parameters. Results: According to DVH analysis, D98 for CTVv and D2 for both CTVs and CTVv showed statistically significant differences between IM-BRT and SC-BRT plans, but there was no significant difference between IM-BRT and MC-BRT plans in terms of D98 and D2 for both CTVs and CTVv. Additionally, for CTVv plans, IM-BRT was found to be significantly superior to SC-BRT for the rectum (D2cc, V5Gy, and V7Gy), bladder (D2cc and V7Gy), and small bowel (D2cc, V5Gy, and V7Gy). On the other hand, DVH parameters of the sigmoid showed large difference between IM-BRT and SC-BRT plans, but it was not statistically significant. Similarly, the use of IM-BRT applicator demonstrated a noticeable dose reduction in all defined OARs when compared with MC-BRT applicator, but statistically significant for the rectum V7Gy (p = 0.03) only. Conclusions: While the IM-BRT applicator is still in pre-clinical phase, our investigation demonstrated the proof-of-concept in real patient treatment plans with promising dosimetric results compared with SC-BRT and MC-BRT plans in selected patient group.

Applicator-guided proton therapy versus multichannel brachytherapy for vaginal vault irradiation.

To dosimetrically compare applicator-guided intensity-modulated proton therapy (IMPT) and multichannel brachytherapy (MC-BRT) for vaginal vault irradiation (VVI) with special focus on dose to organs at risk (OARs) and normal tissues. Ten patients with uterine confined endometrial cancer who received adjuvant vaginal cuff brachytherapy were included in this study. For each patient an additional IMPT treatment plan was created using the same computed tomography dataset and contours segmented for MC-BRT plans. Clinical target volume (CTV) was defined as the proximal 3.5 cm of the vagina including the entire thickness of vaginal wall. Planning target volume for IMPT plans was generated from the CTV with an addition isotropic 3 mm margin. OARs included rectum, bladder, sigmoid, small bowel and femoral heads. The prescribed dose was 21 Gy in 3 fractions. For simplicity, all doses were expressed in Gy and a constant relative biological effectiveness of 1.1 was used for IMPT plans. Plan comparison was performed using dose-volume histogram and treatment planning parameters. A significant improvement of the D98% coverage for CTV was reached by the applicator-guided IMPT plans (p < 0.01). IMPT also provided a dose reduction in all OARs except for femoral heads due to the lateral beam direction, especially significant reduction of V5Gy, D2cc, D0.1 cc, Dmean, V95% values for the rectum and Dmean, D0.1 cc to bladder, sigmoid, small bowel. Additionally, IMPT plans showed a significant reduction of integral dose to normal tissue with respect to MC-BRT (221.5 cGy.L vs. 653.6 cGy.L, p < 0.01). Applicator-guided IMPT has the potential for improving plan quality in VVI while maintaining the high conformity afforded by the state-of-the-art intracavitary brachytherapy.

HIPEC for gynaecological malignancies: A last update (Review).

Advanced-stage gynaecological cancer represents a clinical entity with challenging surgical treatment in an effort to optimize prognosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) following cytoreductive surgery (CRS) has been reported as a method potentially eligible to improve prognosis. However, no definitive conclusions have yet been made on which types of cancer and which context HIPEC may actually have a beneficial impact. The present review discusses the efficacy and safety of HIPEC as a treatment option for patients with primary/recurrent ovarian, endometrial and cervix cancer, as well as peritoneal sarcomatosis. A literature search was conducted using MeSH terms for each topic in the PubMed database and supplemented with a manual search to retrieve additional articles eligible for inclusion/fulfilling the inclusion criteria. The implementation of HIPEC appears to be beneficial in terms of survival in patients with epithelial ovarian carcinoma (EOC) following neoadjuvant chemotherapy, as well as in patients with recurrent EOC. Statistical superiority is not justified by current studies regarding other gynaecological malignancies with peritoneal dissemination. Furthermore, as regards safety, HIPEC following CRS does not appear to significantly increase the mortality and morbidity rates compared to the use of CRS alone. The rationale for using HIPEC and CRS in the treatment of ovarian cancer, particularly in the neoadjuvant setting, as well as for recurrences, is adequately evidenced, with acceptable safety and post-operative complication rate profiles. Its current place in the multimodal strategy for patients with peritoneal metastases remains uncertain, however. Randomized clinical trials are warranted to further examine the use of HIPEC and establish the optimal regimen and temperature settings. The role of optimal cytoreduction and no residual disease, as well as the proper patient selection remain basic parameters for maximizing survival parameters.

Safety of Combined Targeted and Helixor®Viscum album L. Therapy in Breast and Gynecological Cancer Patients, a Real-World Data Study.

BACKGROUND: Newer personalized medicines including targeted therapies such as PARP inhibitors and CDK 4/6 inhibitors have been shown to improve the survival of breast and gynaecological cancer patients. However, efficacy outcomes may be ham5pered by treatment discontinuation due to targeted therapy-related adverse drug reactions or resistance. Studies have suggested that add-on mistletoe (Viscum album L., VA) improves the quality of life and ameliorates the cytotoxic side effects of standard oncological therapy in cancer patients. The primary objective of this real-world data study was to determine the safety profile of targeted therapy in combination with add-on Helixor® VA therapy compared to targeted therapy alone in breast and gynecological cancer patients. METHODS: The present study is a real-world data observational cohort study utilizing demographic and treatment data from the accredited national Network Oncology (NO) registry. The study has received ethics approval. The safety profile of targeted therapies with or without Helixor® VA therapy and safety-associated variables were evaluated by univariate and adjusted multivariable regression analyses. RESULTS: All stages of breast and gynecological cancer patients (n = 242) were on average 54.5 ± 14.2 years old. One hundred and sixty patients (66.1%) were in the control (CTRL, targeted therapy) and 82 patients (33.9%) were in the combinational (COMB, targeted plus Helixor® VA therapy) group. The addition of Helixor® VA did not hamper the safety profile (χ2 = 0.107, p-value = 0.99) of targeted therapy. Furthermore, no adverse events and a trend towards an improved targeted therapy adherence were observed in the COMB group. CONCLUSIONS: The present study is the first of its kind showing the applicability of Helixor® VA in combination with targeted therapies. The results indicate that add-on Helixor® VA does not negatively alter the safety profile of targeted therapies in breast and gynaecological cancer patients.

Effect of adenomyosis on prognosis of patients with endometrial cancer

SUMMARY OBJECTIVE: Our goal was to contrast the prognoses of patients with endometrial cancer who had adenomyosis against those that did not. METHODS: All patients who had received surgical staging for hysterectomy-based endometrial cancer had their medical data retrospectively examined. The analysis covered 397 patients, who were split into two groups depending on the presence of adenomyosis. Comparisons were made between patients covering type of surgery, histopathology, endometrial cancer stage, lymphovascular space invasion, presence of biochemical or histochemical markers, adjuvant therapy, presence of adenomyosis in the myometrial wall, and outcomes in terms of overall survival and disease-free survival. RESULTS: There is no statistically significant difference in the 5-year disease-free survival or overall survival rates between endometrial cancer patients with and without adenomyosis. This is based on comparisons of tumor stage, tumor diameter, histological type and grade of tumor, myometrial invasion, lymphovascular space invasion, and biochemical markers that affect the course of the disease. The median follow-up times were 61 months for the adenomyosis-positive group and 56 months for the group without adenomyosis. CONCLUSION: Coexisting adenomyosis in endometrial cancer has no bearing on survival rates and is not a prognostic factor.

Programmed Cell Death Ligand-1 (PDL-1) Correlates With Tumor Infiltration by Immune Cells and Represents a Promising Target for Immunotherapy in Endometrial Cancer.

BACKGROUND/AIM: Endometrial carcinoma (EC) is one of the most common gynecological cancers in the Western Hemisphere. Nevertheless, there are not enough appropriate treatment options, especially for advanced stages. The immune checkpoint blockade represents a promising alternative to established cancer therapies by suppressing the immune-inhibitory activity of the immune checkpoint factors programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1). In the present study, we characterized the clinical relevance of the biomarker PD-L1 expression in terms of its prognostic capabilities in EC. PATIENTS AND METHODS: Tumor tissue samples from 87 EC patients were retrospectively analyzed by immunohistochemistry (PD-L1, p16, estrogen receptor, progesterone receptor, HER2/neu, Ki-67, CD3, CD20, CD68). RESULTS: A total of 17.3% of EC patients were PD-L1 positive. PD-L1 status did not represent a suitable prognostic marker in EC, but correlated with T3/T4stage, positive lymph node status, p16 expression, and absence of estrogen and progesterone receptor. PD-L1 positive tissues showed increased infiltration with lymphocytes, monocytes, and macrophages, although not statistically significant in every case. CONCLUSION: In EC, PD-L1 expression has no prognostic significance, but correlates with other oncogenic factors and indicates increased infiltration of the tumor with immune cells. Thus, PD-1/PD-L1 immunecheckpoint blockade seems to be very promising, at least in a subset of EC patients.

Adipocyte related peptides - galanin and resistin in endometrioid type endometrium cancer.

OBJECTIVES: The aim of (this) study was to investigate concentrations of galanin and resistin in patients with endometrioid type endometrium cancer. MATERIAL AND METHODS: A total of 85 patients (52 Endometrioid type Endometrium Cancer patients and 33 healthy controls) were included in the study. Serum galanin and resistin levels were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: It was found that the sensitivity and specificity of galanin at the cut off level of 0,37 ng/mL, was 82.96% and 68.78% respectively (AUC = 0.795, CI:0.691-0.898, p < 0.001). Sensitivity and specificity of resistin at the 0.27 ng/mL cut off level, was found to be 82.95% and 59.12% respectively (AUC = 0.705, CI:0.588-0.822, p < 0.001) for prediction of endometrioid type endometrium cancer diagnosis. Bivariate logistic regression analysis showed that, increased galanin concentration, greater than 0.37 ng/mL, increased the risk of having endometrioid type endometrium cancer 10.2 times (95% CI: 3.425-30.881, p < 0.001) and resistin concentration > 0.27 ng/mL, increased the risk of having endometrioid type endometrium cancer 5.6 fold (95% CI: 1.939-16.282, p = 0.001). On the other hand, according to adjusted Odds Ratio results of the multiple logistic regression analysis, effect of interaction between galanin and resistin on having endometrioid type endometrium cancer was statistically significant. Increased galanin concentration > 0.37 ng/mL with increased resistin concentration > 0.27 ng/mL had adjusted Odds Ratio = 27.182 times greater risk of having endometrioid type endometrium cancer (95% CI: 6.653 to 111.109, p < 0.001). CONCLUSIONS: Increased galanin and resistin levels, either separately or together with, seemed to increase the risk of endometrioid type endometrium cancer other than different risk factors.

Synergistic Growth Inhibitory Effects of Eryngium kotschyi Extracts with Conventional Cytotoxic Agents: Cisplatin and Doxorubicin against Human Endometrium Cancer Cells.

BACKGROUND: Endometrial cancer is one of the most common types of cancer. For this reason, various studies have been carried out on its treatment and the effects of natural products on this disease. OBJECTIVES: This study aimed to examine the growth inhibitory effects of Eryngium kotschyi Boiss. ethyl acetate [EKE] and butanol [EKB] obtained from the main methanol [EKM] extract from the aerial parts on human endometrium carcinoma [RL95-2] cells and their synergistic effect with cisplatin or doxorubicin. METHODS: RL95-2 cells were treated with E. kotschyi extracts either alone or in combination with cisplatin or doxorubicin. The effects on cell growth were determined using the MTT assay and real-time cell analysis xCELLigence. RESULTS: The extracts demonstrated growth inhibitory activity, with a certain degree of selectivity against the RL95-2 cell line. Synergistic effects of EKE/cisplatin or doxorubicin at different concentration levels were demonstrated in RL95-2 cells. In some instances, the EKE/doxorubicin combinations resulted in antagonistic effects. The reduction level of cell viability was different and specific to each combination for the RL95-2 cell line. CONCLUSION: The growth inhibitory activity of cisplatin or doxorubicin, as a single agent, may be modified by combinations of the extracts and be synergistically enhanced in some cases. A significant synergistic effect of EKE on the RL95-2 cell line with cisplatin and doxorubicin was observed. This cytotoxic effect can be investigated in terms of molecular mechanisms. This study is the first of its kind in the literature. The mechanisms involved in this interaction between chemotherapeutic drugs and plant extracts remain unclear and should be further evaluated.

Hydroethanolic Extracts of the Aristotelia Chilensis (Maqui) Berry Reduces Cellular Viability and Invasiveness in the Endometrial Cancer Cell Line Ishikawa.

Cancer of the reproductive tract includes diseases with higher prevalence in the female population. This investigation examined whether an anthocyanin-enriched extract of Aristotelia chilensis, commonly known as "maqui," could affect some hallmarks of endometrial cancer. Cultures of the human endometrial cancer cell line Ishikawa were treated with a hydroethanolic maqui extract at 1, 3, 10, 30, 100, 300, or 1000 µg/mL to determine the effect on cell viability by MTT assay. Then, we used the 50% Effective Concentration (EC50) to evaluate whether the effect of the maqui extract is mediated via an arrest of the cell cycle or induction of apoptosis using flow cytometry or Annexin V-FITC assays, respectively. The effects of sublethal doses of the maqui extract on migration and invasiveness of Ishikawa cells were also evaluated by the wound healing and Boyden Chamber assay, respectively. Our results show that the hydroethanolic maqui extract inhibits the cell viability with an EC50 of 472.3 µg/mL via increased apoptosis, and that reduces the invasive capacity but not migration of Ishikawa cells. These findings suggest that the hydroethanolic maqui extract has antineoplastic properties for endometrial cancer and merits further studies to corroborate its efficiency as anticancer therapy in reproductive organs.

Improved disease-free survival with adjuvant radiotherapy in early-stage endometrial cancer: 10-year outcome analysis.

PURPOSE: The purpose of this study was to evaluate long-term treatment outcomes and prognostic factors affecting survival of patients with early-stage endometrial carcinoma. MATERIAL AND METHODS: Data of 311 patients with FIGO stage I-II endometrial cancer, curatively treated at two different tertiary centers between June 2001 and December 2016 were retrospectively reviewed. The patients had primary surgery, 74 (24%) received no further treatment, 4 (1%) obtained chemotherapy only, 234 (75%) received radiotherapy, and 24 (7%) received both. RESULTS: Median follow-up time was 102 (range, 3-205) months. During this period, 68 (21.9%) patients died. 5-year and 10-year disease-free survival (DFS) were 76% and 74.3%, respectively. In multivariate analysis, lower uterine segment invasion positivity and no adjuvant radiotherapy were determined as independent unfavorable prognostic factors for DFS. The 5-year and 10-year disease-specific survival (DSS) were 86.8% and 82.2%, respectively. For DSS, high-grade, lymphovascular space invasion positivity, stage II, ≥ 65 age, and no adjuvant radiotherapy were found to be independent unfavorable prognostic markers. CONCLUSIONS: The findings of our cohort have confirmed the importance of adjuvant radiotherapy on long-term early-stage endometrial carcinoma outcome.

The relationship between KRAS LCS6 polymorphism and endometrium cancer.

The aim of this study was to investigate the relationship between KRAS LCS6 mutation and endometrial cancer (EC). The study included 105 patients who had hysterectomy for benign reasons and 99 EC patients. The patients with Type 1 EC were classified according to histological properties, cancer stage, grade, tumour dimension, myometrial invasion (MMI), lymphovascular invasion (LVI), cytology, and number of positive lymph nodes. KRAS LCS6 mutation was examined in blood samples taken from all patients in both groups. No statistically significant difference was determined between the EC patients and the control group in demographic features. Weight and the Body Mass Index (BMI) values were higher in EC group (p < .001). While the incidence of this polymorphism is 5.8% throughout the world, the polymorphism rate was found to be 16.2% in the EC group and 12.4% in the control group, with no statistically significant difference determined (p > .05). Despite the higher rate of LCS6 polymorphism incidence in EC patients in this study conducted on a relatively large sample, there was not found to be a statistically significant difference in comparison with the control group. In addition, the presence of LCS6 polymorphism was not determined to have an effect on EC histopathological characteristics.Impact statementWhat is already known on this subject? Endometrial cancer (EC) is a genital system cancer which is one of the most widespread gynecological cancers seen in the USA and other developed countries, In EC, the most frequently seen gene mutations are PTEN tumour suppressor gene, KRAS, ß1 catenin, BCL-2, CTNNB and P53 mutations. KRAS LCS6(let-7 miRNA binding region polymorphism) polymorphism has a worldwide incidence of 5.8% (Chin et al. 2008).There are studies shown that KRAS LCS6 polymorphism has an effect on developing EC (Lee et al. 2014), ovarian cancer(Ratner et al. 2010)and endometriosis in women (Grechukhina et al. 2012).What do the results of this study add? In our study, LCS6 located on KRAS 3'-UTR was found at the rate of 16.2% in Type 1 EC patients. This increase is noticeable when it is considered that the incidence of this polymorphism is 5.8% in the general population. The results of the current study supports the preliminary findings of Lee et al.What are the implications of these findings for clinical practice and/or further research? These new genetic markers could help to develop gene-targeted therapies, identify genetic basis of the disease and the factors that could affect the EC prognosis.

Preoperative Serum CA 125 is Associated With Myometrial and Cervical Invasion in Endometrial Carcinoma

@#Introduction: Endometrial carcinoma is the most common gynaecological malignancy in developed countries and the sixth most common cancer among women worldwide. Cancer staging is vital in treatment decisions and the prediction of prognoses, and is based on imaging studies, histological results and surgery. Therefore, a simple and fast preoperative tool to predict the precise cancer stage of patients is needed. CA 125, a cancer antigen, is used in assessing therapeutic response and cancer surveillance in endometrial carcinoma. However, this tumour marker is not routinely performed in the mentioned circumstances. Studies have shown that preoperative CA 125 was significantly high in patients in a higher stage of endometrial cancer. Thus, this study aims to assess the primary role of CA 125 in predicting the stage of endometrial carcinoma, by correlating preoperative serum CA 125 with clinicopathological parameters. Method: The retrospective data of endometrial carcinoma cases consisting of demographic and clinicopathological parameters as well as preoperative serum CA 125 levels were retrieved from Laboratories Information System (LIS) at Hospital Selayang, Selangor, Malaysia, from January 2000 until June 2016. Only 20 cases fulfilled the inclusion and exclusion criteria. Preoperative serum CA 125 was correlated with demographic and clinicopathological parameters, and was analysed using a Kruskal-Wallis test. Results: There was a significant association between elevated serum CA 125 with myometrial and cervical stroma invasion in endometrial carcinoma (p<0.05). Conclusion: Preoperative serum CA 125 is a useful marker in predicting early stages of endometrial carcinoma, and plays a role in pre-operative cancer staging in endometrial carcinoma.

The significance of sonographically thickened endometrium in asymptomatic postmenopausal women.

OBJECTIVE: To investigate the correlation between sonographic, hysteroscopic, and pathological findings in postmenopausal asymptomatic patients with sonographically thickened endometrium. METHODS: The records of postmenopausal patients who attended the Menopause Outpatient Clinic of a tertiary women's hospital in Ankara, Turkey between January 1, 2012 and December 15, 2013 were retrieved. A total of 266 postmenopausal women without vaginal bleeding underwent hysteroscopic evaluation and endometrial sampling. Patients whose pathological records indicated an endometrial thickness equal to or greater than 6 mm (double layer) on transvaginal ultrasonography without any symptoms were included in the study. RESULTS: The most frequently detected focal intrauterine lesions in asymptomatic women were endometrial polyps, which were diagnosed in 168 (63.1%) cases. Twenty-four (9%) patients were diagnosed as having simple hyperplasia, 4 (1%) atypical hyperplasia, and 8 (3%) endometrial adenocarcinoma. Two of the patients with adenocarcinoma were diagnosed based on endometrial polyps, and 6 cases showed endometrial hyperplasia on hysteroscopy, while histological examination showed endometrial carcinoma. CONCLUSION: We suggest 10.5 mm as the cutoff value for endometrial thickness and recommend hysteroscopy following dilatation and curettage to increase diagnostic efficacy and provide definitive treatment in asymptomatic postmenopausal women with thickened endometrium.

Dosimetric comparison of vaginal vault brachytherapy vs applicator-guided stereotactic body radiotherapy with volumetric modulated arc therapy and helical tomotherapy for endometrium cancer patients.

We performed this dosimetric study to compare a nonstandard volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) techniques with high-dose rate (HDR) brachytherapy (BRT) plan of vaginal vault in patients with postoperative endometrial cancer (EC). Twelve postoperative patients with early stage EC were included in this study. Three plans were performed for each patient; dosimetric and radiobiological comparisons were made using dose-volume histograms and equivalent dose for determining the planning target volume (PTV) coverages in brachytherapy and external beam radiotherapy, and organs-at-risk (OARs) doses between three different delivery techniques. All the plans achieved adequate dose coverage for PTV; however, the VMAT plan yielded better dose conformity, and the HT plan showed better homogeneity for target volume. With respect to the OARs, the bladder D2cc was significantly lower in the BRT plan than in the VMAT and HT plans, with the highest bladder D2cc value being observed in the HT plan. However, no difference was observed in the rectum D2cc of the three plans. Other major advantages of the BRT plan over the VMAT and HT plans were the relatively lower body integral doses and femoral head doses as well as the fact that the integral doses were significantly lower in the BRT plan than in the VMAT and HT plans. This is the first dosimetric comparison of vaginal vault treatment for EC with BRT, VMAT, and HT plans. Our analyses showed the feasibility of stereotactic body radiotherapy technique as an alternative to HDR-BRT for postoperative management of EC patients.

The significance of sonographically thickened endometrium in asymptomatic postmenopausal women

OBJECTIVE: To investigate the correlation between sonographic, hysteroscopic, and pathological findings in postmenopausal asymptomatic patients with sonographically thickened endometrium. METHODS: The records of postmenopausal patients who attended the Menopause Outpatient Clinic of a tertiary women's hospital in Ankara, Turkey between January 1, 2012 and December 15, 2013 were retrieved. A total of 266 postmenopausal women without vaginal bleeding underwent hysteroscopic evaluation and endometrial sampling. Patients whose pathological records indicated an endometrial thickness equal to or greater than 6 mm (double layer) on transvaginal ultrasonography without any symptoms were included in the study. RESULTS: The most frequently detected focal intrauterine lesions in asymptomatic women were endometrial polyps, which were diagnosed in 168 (63.1%) cases. Twenty-four (9%) patients were diagnosed as having simple hyperplasia, 4 (1%) atypical hyperplasia, and 8 (3%) endometrial adenocarcinoma. Two of the patients with adenocarcinoma were diagnosed based on endometrial polyps, and 6 cases showed endometrial hyperplasia on hysteroscopy, while histological examination showed endometrial carcinoma. CONCLUSION: We suggest 10.5 mm as the cutoff value for endometrial thickness and recommend hysteroscopy following dilatation and curettage to increase diagnostic efficacy and provide definitive treatment in asymptomatic postmenopausal women with thickened endometrium.

Evaluation of tumor-free distance and depth of myometrial invasion as prognostic factors in endometrial cancer.

The aim of the study was to investigate whether the tumor free distance (TFD), which is the distance in millimeters between the deepest point of invasion and the serosal surface, and absolute depth of invasion (DMI), the distance in millimeters between the endomyometrial junction and the deepest point of myometrial invasion, are useful in surgical staging and in predicting prognosis. The present study retrospectively analyzed 62 cases of endometrial carcinoma with complete surgical staging, carried out over a 4 and half-year period (January 2003 to June 2007). All surgicopathological findings including surgical stages, histological type and grade, myometrial invasion, lymphovascular space invasion, cervical and adnexal involvement, and lymph node metastasis were abstracted from medical records and pathological reports. Univariate and multivariate analyses were performed comparing TFD, DMI and the percentage of mypmetrial invasion (MI) with established prognostic factors. A total of 62 patients were included in the study. A total of 52 (84%) had endometrioid carcinomas and 31 patients (60%) had grade 1 cancer. The deepest MI was <50% in 32 patients (52%). Median DMI was 2.7 mm (range 0-15 mm). Median TFD was 3 mm (range 0-19 mm). There was lymphovascular space invasion (LVSI) in 11 patients (17.5%), cervical involvement in 11 patients (17.5%), extra-uterine extension in 9 cases (14%) and lymph node metastasis in 12 patients (22%). It was demonstrated that 50% MI was significantly associated with prognostic factors (cervical involvement, type 2 carcinomas and LVSI, and was a significant predictor of the 5-year overall survival rate and recurrence-free survival (P=0.05, P=0.01). No significant association was observed between DMI and TFD with clinicopathological parameters and survival rates. The importance of DMI in predicting recurrence of disease was observed to be highest in terms of sensitivity and specificity. The cut-off value with the highest sensitivity and specificity crossing the receive operating characteristic curve was calculated to be 3 mm for DMI and 2.5 mm for TFD. The results indicate that DMI is a superior predictive factor of recurrence of the disease compared with TFD. However, further studies are required in order to prove the prognostic usefulness of these parameters and then to improve management of endometrial cancer.

Independent predictors of survival in endometrium cancer: platelet-to-lymphocyte ratio and platelet/neutrophil/monocyte-to-lymphocyte ratio

Objective: To evaluate the association between ratios of inflammatory markers and survival in endometrium cancer (EC). Material and Methods: Four hundred ninety-seven patients with epithelial EC were included. The evaluated ratios were neutrophil (N)/lymphocyte (L), neutrophil count divided by the lymphocyte count; platelet (P)/lymphocyte, platelets divided by the lymphocyte count; lymphocyte/monocyte (M), lymphocytes divided by the monocyte count; NM/L, neutrophil plus monocyte divided by the lymphocyte count; PNM/L, the sum total counts of platelets, neutrophils and monocytes divided by the lymphocyte count. Results: The median follow-up time was 24 months (1-129). Recurrence and exitus occurred in 34 (7%) and 18 (3.7%) patients, respectively. Metastasis in pelvic or para-aortic lymph nodes were significantly related only with low L/M. None of the inflammatory ratios were associated with disease-free survival. In multi-variant analysis, only high P/L (>168) and high PNM/L (>171) were related with a statistically significant hazard ratio for death of 2.91 (p=0.024) and 2.93 (p=0.023), respectively. Conclusion: The P/L and PNM/L were in relation with worse overall survival and also independent prognostic factors for OS.

α-Chaconine and α-Solanine Inhibit RL95-2 Endometrium Cancer Cell Proliferation by Reducing Expression of Akt (Ser473) and ERα (Ser167).

The aim of this study is to investigate the potential inhibitory effect of α-chaconine and α-solanine on RL95-2 estrogen receptor (ER) positive human endometrial cancer cell line and to identify the effect of these glycoalkaloids on the Akt signaling and ERα. The cell proliferation profiles and the cytotoxicity studies were performed by Real-Time Cell Analyzer (xCELLigence) and compared with Sulphorhodamine B (SRB) assay. The effects of α-chaconine (2.5, 5, 10 µM), α-solanine (20, 30, 50 µM), API-1 (25 µM) and MPP (20 µM) effects on Akt (Ser473) and ERα (Ser167) expressions evaluated by Western blot and qPCR method. Their IC50 values were as α-chaconine (4.72 µM) < MPP (20.01 µM) < α-solanine (26.27 µM) < API-1 (56.67 µM). 10 µM α-chaconine and 20, 30 and 50 µM α-solanine were effective in decreasing p-Akt(Ser473)/Akt ratio compared to positive control API-1. When the p-ERα/ERα ratios were evaluated, it was observed that α-chaconine (2.5, 5, 10 µM) and α-solanine (50 µM) were as effective as the specific ERα inhibitor MPP in reducing the ratio of p-ERα/ERα compared to the control group. In conclusion, it has been shown that the proliferation of α-chaconine and α-solanine in human endometrial carcinoma cells reduces the expression and activity of the Akt and ERα signaling pathway.