Advanced Stage Endometrial Carcinoma Research Articles

Long non-coding RNA JPX promotes endometrial carcinoma progression via janus kinase 2/signal transducer and activator of transcription 3.

Although LncRNA JPX has been linked to a number of malignancies, it is yet unknown how it relates to endometrial carcinoma (EC). Investigating the expression, functional activities, and underlying molecular processes of lncRNA JPX in EC was the goal of this work. RT-qPCR was used to examine the differences in lncRNA/microRNA (miRNA, miR)/mRNA expression between normal cervical and EC tissues or cells. Cell Counting Kit-8, flow cytometry, and transwell were used to evaluate the association between lncRNA JPX/miR-140-3p/phosphoinositide-3-kinase catalytic subunit α (PIK3CA) in Ishikawa and JEC cell lines. The impact of JPX on the downstream janus kinase (JAK)2/signal transducer and activator of transcription (STAT)3 signaling pathway was investigated using Western blot analysis. When comparing EC tissues to nearby normal tissues, JPX expression is markedly increased in EC tissues, with greater expression in advanced-stage EC. Furthermore, compared to normal epithelial cells, EC cell lines have higher levels of JPX expression. In Ishikawa and JEC endometrial cancer cell lines, we used siRNA-mediated suppression of JPX to find lower cell viability, increased apoptosis, cell cycle arrest, and reduced migration and invasion. We next verified that miR-140-3p binds to downstream target cells to impede the transcription and translation of PIK3CA, which in turn prevents the growth of Ishikawa and JEC cells. JPX functions as a ceRNA to adsorb miR-140-3p. This procedure required controlling JAK2/STAT3, a downstream signal. JPX enhances the development of Ishikawa and JEC cells and activates downstream JAK2/STAT3 signal transduction via the miR-140-3p/PIK3CA axis, offering a possible therapeutic target for the treatment of EC.

Prognostic Role of Human Epididymis Protein4 (HE4) in Endometrial Lesions: Study in a Tertiary Care Centre.

Endometrial cancer accounts for 20% of malignant tumours in the female reproductive system. A novel biological marker human epididymis protein4 (HE4) represents an important alternative indicator which may benefit patient mortality. To correlate the immunohistochemical expression of HE4 in different non-neoplastic and neoplastic endometrial lesions and with the WHO grade of the tumours. Our study was a cross-sectional, observational study done in a tertiary care hospital from December 2019 to June 2021 on the hysterectomy sample of 50 patients with a clinical history of abnormal uterine bleeding and pelvic pain. The study showed strong positivity of HE4 in cases of endometrial carcinoma, weak positivity in cases of atypical endometrial hyperplasia, and negativity in cases of endometrial hyperplasia without atypia group. WHO grade 3(50%) and grade 2 (29%) endometrioid adenocarcinoma NOS in our study showed strong positivity for HE4 which was statistically significant (P value = 0.001). In recent studies using overexpression of HE4-related genes, the malignant biological behaviour such as cell adhesion, invasion, and proliferation was enhanced. It was seen in our study that strong positivity of HE4 was seen in all endometrial carcinoma groups and with higher WHO grade. So, HE4 may become a potential therapeutic target for advanced-stage endometrial carcinoma which requires further research. Thus, human epididymis-specific protein 4 (HE4) has been shown to be a promising marker for the detection of endometrial carcinoma patients who could be benefitted from targeted therapy.

Development and Validation of Multiparametric MRI-based Radiomics Models for Preoperative Risk Stratification of Endometrial Cancer.

Background Stratifying high-risk histopathologic features in endometrial carcinoma is important for treatment planning. Radiomics analysis at preoperative MRI holds potential to identify high-risk phenotypes. Purpose To evaluate the performance of multiparametric MRI three-dimensional radiomics-based machine learning models for differentiating low- from high-risk histopathologic markers-deep myometrial invasion (MI), lymphovascular space invasion (LVSI), and high-grade status-and advanced-stage endometrial carcinoma. Materials and Methods This dual-center retrospective study included women with histologically proven endometrial carcinoma who underwent 1.5-T MRI before hysterectomy between January 2011 and July 2015. Exclusion criteria were tumor diameter less than 1 cm, missing MRI sequences or histopathology reports, neoadjuvant therapy, and malignant neoplasms other than endometrial carcinoma. Three-dimensional radiomics features were extracted after tumor segmentation at MRI (T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI). Predictive features were selected in the training set with use of random forest (RF) models for each end point, and trained RF models were applied to the external test set. Five board-certified radiologists conducted MRI-based staging and deep MI assessment in the training set. Areas under the receiver operating characteristic curve (AUCs) were reported with balanced accuracies, and radiologists' readings were compared with radiomics with use of McNemar tests. Results In total, 157 women were included: 94 at the first institution (training set; mean age, 66 years ± 11 [SD]) and 63 at the second institution (test set; 67 years ± 12). RF models dichotomizing deep MI, LVSI, high grade, and International Federation of Gynecology and Obstetrics (FIGO) stage led to AUCs of 0.81 (95% CI: 0.68, 0.88), 0.80 (95% CI: 0.67, 0.93), 0.74 (95% CI: 0.61, 0.86), and 0.84 (95% CI: 0.72, 0.92), respectively, in the test set. In the training set, radiomics provided increased performance compared with radiologists' readings for identifying deep MI (balanced accuracy, 86% vs 79%; P = .03), while no evidence of a difference was observed in performance for advanced FIGO stage (80% vs 78%; P = .27). Conclusion Three-dimensional radiomics can stratify patients by using preoperative MRI according to high-risk histopathologic end points in endometrial carcinoma and provide nonsignificantly different or higher performance than radiologists in identifying advanced stage and deep myometrial invasion, respectively. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kido and Nishio in this issue.

Determinants of Surgical Approach and Survival Among Women with Endometrial Carcinoma

To investigate determinants of surgical approach among women with endometrial carcinoma (EC) and associations between surgical approach and overall survival (OS). Retrospective cohort. The National Cancer Database, 2010 to 2015. A total of 140470 patients with histologically confirmed EC who underwent hysterectomy. Patients were grouped according to surgical approach. A total of 140 470 patients with EC were included. Robotic-assisted laparoscopy (RAL) was the most common surgical approach (48.8%), followed by laparotomy (33.6%) and traditional laparoscopy (17.6%). Use of RAL increased over the study period, and the percentages of cases managed by laparotomy decreased. Older women, those with insurance, residing in ZIP codes with lower proportions of individuals who did not graduate from high school, and those treated at noncommunity cancer programs were less likely to undergo laparotomy than RAL, and non-white women, those diagnosed with high-grade histology, and those with advanced-stage EC were more likely to undergo laparotomy than RAL. Compared with RAL, all other surgical approaches were associated with worse OS (laparotomy: hazard ratio 1.21; 95% confidence interval, 1.18-1.25; traditional laparoscopy: hazard ratio 1.06; 95% confidence interval, 1.02-1.09). Significant effect modification of the surgical approach and OS relationship according to age, race, histology, stage, and adjuvant treatment was observed. RAL increased in frequency over the study period and was associated with improved OS, supporting the continued use of RAL for EC management.

Phosphoproteomic response mapping to anti-angiogenic agents bevacizumab and cediranib in high-grade serous ovarian and endometrial cancer cell lines

<h3>Objectives:</h3> Antiangiogenics have become a cornerstone of treatment in advanced stage and recurrent high grade serous ovarian cancer. Both cediranib (ICON6) and bevacizumab (ICON7, GOG218) have demonstrated benefit as a maintenance treatment for ovarian cancer patients in clinical trials. Investigators have also explored their role in advanced stage and recurrent endometrial carcinoma (MITO-END 2, Rose 2017, Aghajanian 2011). There have been no head to head trials in gynecologic cancers comparing cediranib to bevacizumab, although in colorectal carcinoma, phase III data suggests equivalent efficacy (HORIZON III). We hypothesize that these drugs, although both categorized as anti-angiogenics, induce unique cellular responses and sought to explore the varying impact of each agent on cell signaling using established serous cell models. <h3>Methods:</h3> CAOV3 ovarian cancer cells and Hec50 endometrial cancer cells were exposed to 1µM bevacizumab or cediranib for 24 hours. Cell lysates were analyzed in duplicate using an antibody-based phosphoproteomic array of 875 phosphoproteins supplied by Kinexus Bioinformatics (Vancouver, BC). Priority signaling effects were defined for each drug and in each cell line as those with a significant (>75%) change from control with an acceptable sum of error (<75%). <h3>Results:</h3> Bevacizumab yielded 13 total leads, and cediranib yielded 9 in CAOV3 ovarian cancer cells (Table 1). Both agents significantly enhanced signaling events on the following epitopes: ABl, EZH2, HGK (2 sites), and IGF1R, indicating that these may be some of the core cellular effects of anti-angiogenic agents. Interestingly, all common leads induced by both agents in CAOV3 cells represent potential pro-oncogenic effects. In Hec50 cells (Table 1), both cediranib and bevacizumab treatment induced a unique set of phosphoproteins compared to the effects of these agents in CAOV3 cells, yet common findings were the phosphorylation of IGFR1 by bevacizumab and the activation of alternative MAP kinases in both cell lines. <h3>Conclusions:</h3> Angiogenesis plays a crucial role in tumor development and metastasis. Blocking angiogenesis using monoclonal antibodies such as bevacizumab or tyrosine kinase inhibitors such as cediranib is a strategy that is proving to be helpful in the care of patients with gynecologic malignancies. These molecular agents have both on-target, therapeutic effects but also may induce pathways of resistance. In these comprehensive phosphoproteomic mapping studies, we noted the activation of signaling pathways which were cell and drug specific. One consistent finding was the enhanced phosphorylation of IGFR1 and alternative MAP kinases that may portend eventual drug resistance.

Chemotherapy response score as a prognostic tool in patients with advanced stage endometrial carcinoma treated with neoadjuvant chemotherapy

BackgroundChemotherapy response score (CRS) applied to interval debulking specimens quantifies histopathologic response to neoadjuvant chemotherapy in patients with advanced ovarian carcinoma and correlates with progression-free and overall survival.ObjectiveTo investigate whether...

Reproducibility of scoring criteria for HER2 immunohistochemistry in endometrial serous carcinoma: a multi-institutional interobserver agreement study.

Targeted anti-human epidermal growth factor receptor 2 (HER2) therapy has recently been proven to improve progression-free and overall survival of patients with advanced stage or recurrent endometrial serous carcinoma. To date, no specific pathology HER2 testing or scoring guidelines exist for endometrial cancer. However, based on evidence from the recent successful clinical trial and comprehensive pre-trial pathologic studies, a new set of HER2 scoring criteria have been proposed for endometrial serous carcinoma-distinct from the existing breast and gastric cancer-specific criteria. We present the first study assessing interobserver agreement of HER2 scores using the proposed serous endometrial cancer-specific scoring system. A digitally scanned set of 40 HER2-immunostained slides of endometrial serous carcinoma were sent to seven gynecologic pathologists, who independently assigned HER2 scores for each slide following a brief tutorial. Follow-up fluorescent in situ hybridization (FISH) for HER2 gene amplification was performed on cases with interobserver disagreement when a 2+ HER2 score was assigned by at least one observer. Complete agreement of HER2 scores among all 7 observers was achieved on 15 cases, and all but one case had an agreement by at least 4 observers. The overall agreement was 72.3% (kappa 0.60), 77.5% (kappa 0.65), and 83.3% (kappa 0.65), using four (0 to 3+ ), three (0/1+ , 2+ , 3+ ), or two (0/1+ , 2/3+ ) HER2 scoring categories, respectively. Based on the combination of HER2 immunostaining scores and FISH, the interobserver disagreement may have potentially resulted in a clinically significant difference in HER2 status only in three tumors. We conclude, that the proposed serous endometrial cancer-specific HER2 scoring criteria are reproducible among gynecologic pathologists with moderate to substantial interobserver agreement rates comparable to those of previously reported in breast and gastric carcinomas. Our findings significantly strengthen the foundation for establishing endometrial cancer-specific HER2 scoring guidelines in the future.

HER2 Testing and Reporting in Endometrial Serous Carcinoma: Practical Recommendations for HER2 Immunohistochemistry and Fluorescent In Situ Hybridization: Proceedings of the ISGyP Companion Society Session at the 2020 USCAP Annual Meeting.

Anti-HER2 therapy has recently emerged as an effective targeted treatment approach for patients with advanced stage and recurrent endometrial serous carcinoma, resulting in significantly prolonged progression-free and overall survival when combined with the standard chemotherapy regimen. Consequently, there is an increasing clinical demand in pathology laboratories for HER2 testing of these tumors. This article provides an overview of the unique characteristics of HER2 protein expression and gene amplification in endometrial serous carcinoma and summarizes the HER2 scoring criteria used for patient enrollment in the recent clinical trial. Following the experience of guideline-development in other tumor types, the trial criteria should serve as the basis for future endometrial carcinoma-specific HER2 testing and scoring recommendations, to ensure therapeutic response in new patient cohorts. Thus, based on the clinical trial, the author proposes a specific HER2 testing algorithm for endometrial serous carcinoma to guide the current clinical practice. Future studies are necessary to refine and adjust these criteria to allow for appropriate triaging of patients and maximize the clinical benefit from HER2-targeted therapy.

Interobserver diagnostic reproducibility in advanced-stage endometrial carcinoma.

BackgroundThe accurate pathologic diagnosis and subtyping of high-grade endometrial carcinoma are often problematic, due to its atypical and overlapping histopathological features.MethodsThree pathologists reviewed 21 surgically resected cases of advanced-stage endometrial carcinoma. The primary diagnosis was based only on hematoxylin and eosin stained slides. When a discrepancy arose, a secondary diagnosis was made by additional review of immunohistochemical (IHC) stains. Finally, three pathologists discussed all cases and rendered a consensus diagnosis.ResultsThe primary diagnoses were identical in 13/21 cases (62%). The secondary diagnosis based on the addition of IHC results was concordant in four of eight discrepant cases. Among four cases with discrepancies occurring in this step, two cases subsequently reached a consensus diagnosis after a thorough discussion between three reviewers. Next-generation sequencing (NGS) study was performed in two cases in which it was difficult to distinguish between serous carcinoma and endometrioid carcinoma. Based on the sequencing results, a final diagnosis of serous carcinoma was rendered. The overall kappa for concordance between the original and consensus diagnosis was 0.566 (moderate agreement).ConclusionsWe investigated stepwise changes in interobserver diagnostic reproducibility in advanced-stage endometrial carcinoma. We demonstrated the utility of IHC and NGS study results in the histopathological diagnosis of advanced-stage endometrial carcinoma.

Treatment Outcomes of Advanced Stage Endometrial Carcinoma (Stage III-IV) and Related Factors

Objective: The aim of this study was to determine treatment response, the recurrence rate, 3-year overall survival, 3-year recurrence-free survival, and associated prognostic factors for survival among advanced-stage endometrial carcinoma patients at Siriraj Hospital. Methods: This study was conducted at the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University Bangkok, Thailand. A total of 415 patients that were diagnosed with advanced-stage endometrial carcinoma during January 1998 to December 2014 were enrolled. Data retrieved from medical records included baseline characteristics, surgico-pathological reports, treatment protocol, follow-up data, treatment response, and recurrence status. Three-year survival and recurrence-free survival were estimated by Kaplan-Meier method. Various factors were analyzed for significant association with survival. Results: Four hundred of 415 cases were included in the final analysis. There were 282 (70.5%) and 118 (29.5%) patients that were diagnosed with stage III and IV disease, respectively. Two hundred and eighty-two patients had complete response after primary treatment, and 94 (33.3%) patients had disease recurrence. The median follow-up and survival times were 24.5 and 42.5 months, respectively. The 3-year survival rate was 50%, and the median recurrence-free interval was 12.25 months. Multivariate analysis revealed high-grade tumor histology, lymph node metastasis, Eastern Cooperative Oncology Group (ECOG) performance status, and menopausal status to be significant prognostic factors for overall survival. Conclusion: Median survival among patients with advanced-stage endometrial carcinoma after primary treatment was 3 years. The significant prognostic factors were high grade tumor histology, lymph node metastasis, ECOG performance status, and menopausal status.

Comparison of Adjuvant Radiation Treatment and Chemotherapy Sequencing in Women with Advanced Stage Endometrial Carcinoma

There remains no definitive consensus on the optimal sequencing of adjuvant chemotherapy (CT) and radiotherapy (RT) for women with stage III endometrial carcinoma. Recurrence-free (RFS), disease-specific (DSS) and overall survival (OS) endpoints were compared between women who received RT concurrent with cisplatin followed by 4 more cycles of CT (carboplatin and paclitaxel) and those who received 3 cycles of CT (carboplatin and paclitaxel) then RT alone then 3 more cycles of CT (“sandwich” technique). After IRB approval, we analyzed the data of 140 women with FIGO stage III disease treated from 1/1995 to 12/2017 at our institution. All women were surgically staged and received adjuvant combined modality therapy with different sequences (concurrent or “sandwich”). Differences in variables between the two arms were assessed by chi-squared test. Survival endpoints were assessed by Kaplan-Meier and log-rank tests. Univariate (UVA) and multivariate (MVA) models with Cox regression analyses were generated to determine significant predictors for survival endpoints. Of the 140 women included, 66 (47%) received the “sandwich” technique and 74 (53%) received concurrent therapy. Median follow-up was 43.7 months. There were 77 women (55%) with uterine endometrioid carcinoma and 111 women (80%) with stage IIIC disease. The concurrent group was found to have a significantly better 5-year RFS rate (Hazard Ratio [HR]=0.70, 95% Confidence Interval [CI] 0.46-0.85) compared to the sandwich technique (HR 0.47 [0.33-0.6], p=0.02). There was no statistically significant difference in the pattern of recurrence between the two groups. On MVA, significant predictors of worsened RFS were higher comorbidity burden (Charlson score)(p=0.02), grade 3 vs 2 (p=0.01), FIGO stage IIIC disease (p=0.04), and lower uterine segment involvement (p=0.001). There was no statistically significant difference found between the two groups in regards to OS and DSS. This study suggests that the sequence of radiation therapy given concurrently with chemotherapy is relatively better in terms of recurrence-free survival in women with stage III endometrial carcinoma compared to the “sandwich” approach. These data warrant further validation in a multi-institutional prospective study.

Histopathologic features of advanced stage endometrial carcinoma

Histopathologic features of advanced stage endometrial carcinoma

Impact of Adjuvant Modalities on Survival in Patients with Advanced Stage Endometrial Carcinoma: A Retrospective Analysis from a Tertiary Medical Center.

Adjuvant treatment in advanced-stage (stages III /IV) endometrial carcinomas in terms of tumor grades has not yet been explored. We retrospectively analyzed 194 patients with advanced-stage endometrioid endometrial carcinoma who received surgery, followed by adjuvant therapy, at National Taiwan University Hospital between January 1, 2000 and August 31, 2017. Adjuvant therapies included radiation (RT), chemotherapy alone (CT), and combined modality treatment (CMT: radiation and chemotherapy). The prognostic factors were determined from multivariate survival analyses using Cox regression models. Progression-free survival (PFS) and overall survival (OS) times were estimated with the Kaplan–Meier method. The median follow-up was 45.5 months (range: 6.2–207.9). In grade 1/2 endometrioid carcinoma, neither adjuvant CT nor CMT could prolong PFS significantly compared to RT (CT: HR 1.59, 95% CI 0.64–3.97; CMT: HR 2.03, 95% CI 0.72–5.74). Notably, maximal cytoreduction independently improved PFS (HR 0.31, 95% CI 0.10–0.90). No particular adjuvant treatment provided an OS advantage over the others for grade 1/2 endometrioid carcinomas. However, for grade 3 endometrioid carcinoma, CMT showed OS benefits (HR 0.15, 95% CI 0.03–0.89) compared to RT and CT. In conclusion, maximal cytoreduction should be the goal in patients with grade 1/2 advanced-stage endometrioid carcinomas. Based on our results, patients with grade 3 endometrioid carcinomas might benefit from adjuvant CMT.

Impact of Adjuvant Modalities on Survival in Patients with Advanced Stage Endometrial Carcinoma: A retrospective analysis from a tertiary medical center

Impact of Adjuvant Modalities on Survival in Patients with Advanced Stage Endometrial Carcinoma: A retrospective analysis from a tertiary medical center

Does Age-Adjusted Charlson Comorbidity Score Impact Survival Endpoints in Women with Federation of Gynecology and Obstetrics-Stage III Endometrial Cancer?

Objectives: We sought to evaluate the impact of age-adjusted Charlson comorbidity index (AACCI) score on survival endpoints for women with advanced stage endometrial carcinoma (EC). Methods and Materials: We identified 238 women with stage III EC. AACCI score was calculated and 3 groups were created accordingly; group 1 with a score of 0–2, group 2 with score 3–4, and group 3 with score ≥5. Significant predictors of recurrence-free (RFS), disease-specific (DSS) and overall survival (OS) were analyzed. Results: Median follow-up was 54 months and median age was 65 years. Stage IIIC was the most common stage (69%). The 3 groups were well-balanced except for less utilization of adjuvant chemotherapy in group 3 (p = 0.01). Five-year OS was significantly lower in group 3 compared to groups 1 and 2 (23 vs. 65 and 51%, respectively). Similarly, 5-year RFS was 54, 41, and 33% and DSS was 65, 54, and 35% for groups 1, 2, and 3 respectively. On multivariate analyses, AACCI group 3, cervical stromal involvement, positive peritoneal cytology, and higher tumor grade were predictors for shorter OS. Cervical stromal involvement and higher grade were independent predictors for worse RFS and DSS. Additionally, positive cytology, lymphovascular space invasion, and stage IIIC2 were significantly detrimental for RFS. Conclusions: Our study suggests that comorbidity burden is a strong predictor of worse OS in women with stage III EC. Women with higher AACCI are less likely to receive adjuvant chemotherapy. Comorbidity score can significantly impact survival endpoints for women with advanced EC.

Loss of CD73-mediated actin polymerization promotes endometrial tumor progression.

Ecto-5'-nucleotidase (CD73) is central to the generation of extracellular adenosine. Previous studies have highlighted a detrimental role for extracellular adenosine in cancer, as it dampens T cell-mediated immune responses. Here, we determined that, in contrast to other cancers, CD73 is markedly downregulated in poorly differentiated and advanced-stage endometrial carcinoma compared with levels in normal endometrium and low-grade tumors. In murine models, CD73 deficiency led to a loss of endometrial epithelial barrier function, and pharmacological CD73 inhibition increased in vitro migration and invasion of endometrial carcinoma cells. Given that CD73-generated adenosine is central to regulating tissue protection and physiology in normal tissues, we hypothesized that CD73-generated adenosine in endometrial carcinoma induces an innate reflex to protect epithelial integrity. CD73 associated with cell-cell contacts, filopodia, and membrane zippers, indicative of involvement in cell-cell adhesion and actin polymerization-dependent processes. We determined that CD73-generated adenosine induces cortical actin polymerization via adenosine A1 receptor (A1R) induction of a Rho GTPase CDC42-dependent conformational change of the actin-related proteins 2 and 3 (ARP2/3) actin polymerization complex member N-WASP. Cortical F-actin elevation increased membrane E-cadherin, β-catenin, and Na(+)K(+) ATPase. Together, these findings reveal that CD73-generated adenosine promotes epithelial integrity and suggest why loss of CD73 in endometrial cancer allows for tumor progression. Moreover, our data indicate that the role of CD73 in cancer is more complex than previously described.

Para-aortic and pelvic extended-field radiotherapy for advanced-stage uterine cancer: dosimetric and toxicity comparison between the four-field box and intensity-modulated techniques.

In patients with advanced-stage endometrial carcinoma (eca), extended-field radiotherapy (efrt) is traditionally delivered by the 3-dimensional conformal (3d-crt) 4-field box technique. In recent years, the use of intensity-modulated radiotherapy (imrt) in gynecologic cancers has increased. We compared the delivery of efrt by the 3d-crt and contemporary imrt techniques. After surgical staging and adjuvant chemotherapy in 38 eca patients, efrt was delivered by either imrt or 3d-crt. Doses to the organs at risk, side effects, and outcomes were compared between the techniques. Of the 38 eca patients, 33 were stage iiic, and 5 were stage ivb. In the imrt group, maximal doses to rectum, small intestine, and bladder were significantly higher, and mean dose to bladder was lower (p < 0.0001). Most acute gastrointestinal, genitourinary, and hematologic side effects were grade i or ii and were comparable between the groups. In long-term follow-up, only grade 1 cystitis at 3 months was statistically higher in the imrt patients. No grade iii or iv gastrointestinal or genitourinary toxicities were observed. No statistically significant differences in overall and disease-free survival or recurrence rates were observed between the techniques. In advanced eca patients, imrt is a safe and effective technique for delivering efrt to the pelvis and para-aortic region, and it is comparable to the 3d-crt 4-field box technique in both side effects and efficacy. For centres in which imrt is not readily available, 3d-crt is a valid alternative.

Expression and clinical significance of annexin A2 and human epididymis protein 4 in endometrial carcinoma.

BackgroundIt is well-known that the treatment and monitoring methods are limited for advanced stage of endometrial carcinoma. Biological molecules with expression changes during tumor progression become potential therapeutic targets for advanced stage endometrial carcinoma. Annexin A2 (ANXA2) has been reported to be overexpressed in recurrent endometrial carcinoma, and the expression of human epididymis protein 4 (HE4) is upregulated in endometrial carcinoma. What’s more, ANXA2 and HE4 interacted in ovarian cancer and promoted the malignant biological behavior. We speculated that their interaction may exist in endometrial carcinoma as well. We evaluated the expression and the correlation relationship of ANXA2 and HE4 in endometrial carcinoma.MethodsThe expression of ANXA2 and HE4 protein in 84 endometrial carcinoma, 30 endometrial atypical hyperplasia, and 18 normal endometrial tissue samples were then measured using an immunohistochemical assay in paraffin embedded endometrial tissues. The structural relationship between ANXA2 and HE4 was explored by immunoprecipitation and double immunofluorescent staining.ResultsANXA2 and HE4 co-localized in both endometrial tissues and endometrial carcinoma cells. ANXA2 and HE4 were expressed in 95.2 % and 85.7 % of the the endometrial carcinoma, respectively, which were significantly higher than normal endometrium (55.6 % and 16.7 %, both p < 0.05). The expression of ANXA2 and HE4 was significantly correlated with FIGO stage, degree of differentiation, myometrial invasion, and lymph node metastasis. ANXA2 was an independent risk factor for the prognosis of endometrial carcinoma (p < 0.05, hazard ratio [HR] = 8.004). The expression of ANXA2 and HE4 was positively correlated (Spearman correlation coefficient = 0.228, p < 0.05). HE4 was an independent factor for ANXA2 in multivariate linear regression model (p < 0.05).ConclusionWe revealed the co-localization of ANXA2 and HE4 in endometrial carcinoma. Expression levels of ANXA2 and HE4 were closely related to the malignant biological behavior of endometrial carcinoma, and ANXA2 was an independent risk factor for poor prognosis. The expression of ANXA2 and HE4 can affect each other.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0208-8) contains supplementary material, which is available to authorized users.

Neo-adjuvant chemotherapy for advanced stage endometrial carcinoma: a glimmer of hope in select patients.

The objective of this review is to conduct a critical appraisal of the published literature on the use of neo-adjuvant chemotherapy followed by interval debulking in the treatment of stage IVb endometrial carcinoma patients. Narrative review of the pertinent literature on the application of neo-adjuvant chemotherapy and interval surgery in the treatment of advanced stage endometrial cancers. Advanced stage endometrial carcinoma patients are treated by aggressive cytoreduction followed by adjuvant chemotherapy or by chemotherapy alone. The prognosis of patients that cannot undergo surgery is extremely poor. Preoperative reduction of tumor burden by chemotherapy can facilitate surgery in patients previously considered to have an unresectable disease, identify patients with chemo-sensitive tumors that are more likely to benefit from surgery, and enable a less aggressive surgery thus reducing morbidity. However, only 106 cases of neo-adjuvant chemotherapy were documented in the last two decades, majority (76) were described in retrospective case reports and case series. The available data may indicate feasibility of neo-adjuvant treatment in select patients. Compared to patients that had primary surgery, neo-adjuvant setting was associated with improved or equivalent survival and maximal debulking rates and reduced postoperative morbidity. Until further progress is reached, consideration can be given to recommending neo-adjuvant chemotherapy followed by interval debulking to patients with poor performance status or those patients who the surgeon believes would have suboptimal debulking if surgery was attempted.

Risk-stratification of endometrial carcinomas revisited: A combined preoperative and intraoperative scoring system for a reliable prediction of an advanced disease

ObjectiveThe aim of this study is to develop a risk-scoring system for predicting lymph node and distant metastasis in endometrial carcinoma. MethodsA total of 1166 patients, treated at a single institution between 1-2007 and 12-2013, were included in the study. The association of stage IIIC–IV disease with demographic factors (age, body mass index), biochemical factors (complete blood count, serum CA125), preoperative histology and tumor size was examined in unadjusted analyses. Logistic regression analysis was used for the identification of variables that independently predict an advanced disease. ResultsThrombocytosis, serum CA125>35U/mL, preoperative high-risk histology (nonendometrioid or grade 3 endometrioid carcinoma) and tumor size ≥3cm were independently associated with an advanced disease. These predictors were internally validated by a bootstrapping method with statistical significance. A risk-scoring system with an area under the receiver operating characteristic curve of 0.852 (95% confidence interval, 0.821–0.883) was developed. Total risk score points ranged from 0 to 8 for individual patients. With a cut-off of 1 point, stratifying 66.3% of patients to surgical staging, the model predicted stage IIIC–IV carcinomas with a sensitivity of 100%, specificity of 38.0%, positive predictive value of 17.1%, and negative predictive value of 100%. With the same cut-off, the corresponding values were 100%, 34.7%, 16.5% and 100% in predicting stage IIIC carcinomas in a subgroup that underwent lymphadenectomy and had a stage I–IIIC disease. ConclusionsThis risk-scoring system is highly sensitive in predicting an advanced stage endometrial carcinoma at a cut-off of risk score points that is associated with an acceptable lymphadenectomy rate.