High-risk Endometrial Carcinomas Research Articles

Mixed Endometrial Epithelial Carcinoma: Epidemiology, Treatment and Survival Rates-A 10-Year Retrospective Cohort Study from a Single Institution.

Mixed endometrial carcinoma (MEEC) refers to rare endometrial tumours that are composed of two or more distinct histotypes, at least one of which is serous or clear cell. The aim of this study was to evaluate the epidemiology, treatment outcomes and survival rates of patients with mixed endometrial carcinoma. The medical records of 34 patients diagnosed with MEEC between March 2010 and January 2020 were reviewed retrospectively. Clinicopathological variables and treatment strategies were assessed, and overall survival and disease-free survival rates were evaluated. The histology of endometrioid and serous component was found in 26 (76.5%) patients, followed by serous and clear-cell components (5/34, 14.5%) and mixed endometrioid serous and clear-cell components (3/34, 8.8%). The median age at diagnosis was 70 years (range 52-84), and the median follow-up time was 55 months. The 5-year disease-free survival and the 5-year overall survival were 50.4% and 52.4%, respectively. Advanced disease stage was identified as an independent predictor of inferior disease-free (<0.003) and overall survival (p < 0.001). Except for stage, none of the traditional prognostic factors was associated with disease recurrence or death from disease. MEECs represent rare high-risk endometrial carcinomas with significant diagnostic and treatment challenges. Undoubtedly, the implementation of a molecular analysis can offer further diagnostic and management insights.

Therapeutic Benefit of Systematic Lymphadenectomy in Node-Negative Uterine-Confined Endometrioid Endometrial Carcinoma: Omission of Adjuvant Therapy

Simple SummaryEndometrial cancer is the most common gynecological tract malignancy in developed countries. Extrauterine disease, in particular lymph node metastasis, is an important prognostic factor. Nevertheless, pelvic lymphadenectomy is not considered to have a therapeutic benefit, as it did not improve survival in randomized studies. However, lymphadenectomy may have a therapeutic benefit if adjuvant therapy can be omitted without decreasing oncological outcomes, as the long-term quality of life is maintained by avoiding morbidities associated with adjuvant therapy. In intermediate- and high-risk endometrioid endometrial carcinomas, adjuvant therapy may be safely omitted without decreasing long-term survival by open surgery including systematic pelvic and para-aortic lymphadenectomy when patients are node-negative. Systematic lymphadenectomy may remove undetectable low-volume lymph node metastasis in both pelvic and para-aortic regions, and open surgery may reduce vaginal recurrence even without vaginal brachytherapy. However, lymphadenectomy may not improve survival in elderly patients and patients with p53-mutant tumors.Endometrial cancer is the most common gynecological tract malignancy in developed countries, and its incidence has been increasing globally with rising obesity rates and longer life expectancy. In endometrial cancer, extrauterine disease, in particular lymph node metastasis, is an important prognostic factor. Nevertheless, pelvic lymphadenectomy is not considered to have a therapeutic benefit, as it did not improve survival in randomized studies. However, lymphadenectomy may have a therapeutic benefit if adjuvant therapy can be omitted without decreasing oncological outcomes, as the long-term quality of life is maintained by avoiding morbidities associated with adjuvant therapy. In intermediate- and high-risk endometrioid endometrial carcinomas, adjuvant therapy may be safely omitted without decreasing long-term survival by open surgery including systematic pelvic and para-aortic lymphadenectomy when patients are node-negative. Systematic lymphadenectomy may remove undetectable low-volume lymph node metastasis in both pelvic and para-aortic regions, and open surgery may reduce vaginal recurrence even without vaginal brachytherapy. However, lymphadenectomy may not improve survival in elderly patients and patients with p53-mutant tumors. In this review, I discuss the characteristics of lymph node metastasis, the methods of lymph node assessment, and the therapeutic benefits of systematic lymphadenectomy in patients with intermediate- and high-risk endometrioid endometrial carcinoma.

Endometrial Cancer Molecular Characterization: The Key to Identifying High-Risk Patients and Defining Guidelines for Clinical Decision-Making?

Simple SummaryEndometrial carcinomas (EC) have been traditionally classified based on histopathology (types I and II). Determining the risk of a patient to experience disease recurrence is important to decide which patients need adjuvant treatment. The current endometrial carcinoma risk assessment approaches fail to accurately classify patients into low-and high-risk groups. Several studies suggest that combining molecular characteristics with the current risk classification in EC may improve patients’ stratification and treatment decision-making. In this review, we describe how evolving molecular trends can be used as prognostic factors to identify high-risk EC subpopulations. We also look at how the most recent patient-derived models can help researchers find new possible targets and treatments for EC patients.Endometrial carcinomas (EC) are the sixth most common cancer in women worldwide and the most prevalent in the developed world. ECs have been historically sub-classified in two major groups, type I and type II, based primarily on histopathological characteristics. Notwithstanding the usefulness of such classification in the clinics, until now it failed to adequately stratify patients preoperatively into low- or high-risk groups. Pieces of evidence point to the fact that molecular features could also serve as a base for better patients’ risk stratification and treatment decision-making. The Cancer Genome Atlas (TCGA), back in 2013, redefined EC into four main molecular subgroups. Despite the high hopes that welcomed the possibility to incorporate molecular features into practice, currently they have not been systematically applied in the clinics. Here, we outline how the emerging molecular patterns can be used as prognostic factors together with tumor histopathology and grade, and how they can help to identify high-risk EC subpopulations for better risk stratification and treatment strategy improvement. Considering the importance of the use of preclinical models in translational research, we also discuss how the new patient-derived models can help in identifying novel potential targets and help in treatment decisions.

Immunohistochemical Expression of “L1 cell Adhesion Molecule” in Endometrial Carcinomas

BACKGROUND: Endometrial cancer is the most common cancer of the female genital tract. No effective biomarkers currently exist to allow for an efficient risk classification of endometrial carcinoma or to direct treatment (adjuvant radiation and/or chemotherapy) or to triage pelvic and para-aortic lymphadenectomy. L1 cell adhesion molecule (L1CAM) a transmembrane protein of the immunoglobulin family that has been implicated in promoting tumor cell proliferation, migration, invasion, and metastasis became an attractive candidate as a potential biomarker in endometrial carcinoma and potential therapeutic target in high-risk groups.&#x0D; OBJECTIVES: Evaluation of L1CAM expression in endometrial carcinoma and correlation of this expression with various pathological parameters.&#x0D; MATERIALS AND METHODS: Immunohistochemical staining for L1CAM was performed on paraffin-embedded sections of 80 cases of endometrial carcinomas that underwent total hysterectomy with bilateral salpingo-oophorectomy. Expression of L1CAM in &gt;10% of tumor cells was interpreted as positive.&#x0D; RESULTS: L1CAM expression was detected in 22.5% of cases and showed statistically significant correlation with non-endometrioid histological type, high grade, high FIGO stage, high pathological (T) stage, cervical involvement, nodal metastasis, lymphovascular space invasion, and high-risk tumor according to the European Society for Medical Oncology system for risk stratification (p &lt; 0.05).&#x0D; CONCLUSION: The high rate of L1CAM expression in high-risk endometrial carcinomas suggests that L1CAM represents a potential marker for the identification of patients needing closer follow-up and aggressive treatment. In addition, its potential role as a therapeutic target for high-risk endometrial cancer seems promising.

Prognostic importance of DNA ploidy in non-endometrioid, high-risk endometrial carcinomas.

The present study investigated the predictive and prognostic impact of DNA ploidy together with other well-known prognostic factors in a series of non-endometrioid, high-risk endometrial carcinomas. From a complete consecutive series of 4,543 endometrial carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stages I-IV, 94 serous carcinomas, 48 clear cell carcinomas and 231 carcinosarcomas were selected as a non-endometrioid, high-risk group for further studies regarding prognosis. The impact of DNA ploidy, as assessed by flow cytometry, was of particular focus. The age of the patients, FIGO stage, depth of myometrial infiltration and tumor expression of p53 were also included in the analyses (univariate and multivariate). In the complete series of cases, the recurrence rate was 37%, and the 5-year overall survival rate was 39% with no difference between the three histological subtypes. The primary cure rate (78%) was also similar for all tumor types studied. DNA ploidy was a significant predictive factor (on univariate analysis) for primary tumor cure rate, and a prognostic factor for survival rate (on univariate and multivariate analyses). The predictive and prognostic impact of DNA ploidy was higher in carcinosarcomas than in serous and clear cell carcinomas. In the majority of multivariate analyses, FIGO stage and depth of myometrial infiltration were the most important predictive (tumor recurrence) and prognostic (survival rate) factors. DNA ploidy status is a less important predictive and prognostic factor in non-endometrioid, high-risk endometrial carcinomas than in the common endometrioid carcinomas, in which FIGO and nuclear grade also are highly significant and important factors.

Does minimally invasive surgery compromise the oncologic outcome of women with high-risk non-endometrioid endometrial carcinomas

Objectives: To assess outcome in patients with high-risk non-endometrioid endometrial carcinomas undergoing minimally invasive surgical (MIS) approaches compared to laparotomy (LAP).

Hormone receptor expression and risk of recurrence in patients with high-risk endometrial carcinoma treated with chemotherapy.

e15502 Background: Poor long-term survival in high-risk endometrial cancer patients attests to a need for new therapeutic strategies. The prevalence of estrogen (ER) and progesterone receptors (PR) among high-risk endometrial carcinomas has not been systematically studied and is a target to which individualized therapies may be tailored. Methods: 41 women with high grade, stage III/IV and/or aggressive histology endometrial cancer who received post-hysterectomy chemotherapy were identified. Patient, tumor and treatment characteristics were recorded. Immunohistochemical staining of ER and PR was scored on a 0-4 scale incorporating intensity and extent of expression. Receptor-positivity was defined as a score of &gt;= 2. Univariate and multivariate logistic regression analysesand the Cox proportional hazards model were performed to examine hormone receptor expression and recurrence risk. Results: Median age at surgery was 59 years (range 34-79). Median follow up time was 39 months (range 1-82). Recurrence occurred in 21 women (51%) with median time to first recurrence of 19 months (range 1-71). 22 cancers (54%) were ER+ and 21 (51%) PR+. Median ER and PR expression was 2 and 2, respectively (range 0-4). While ER and PR were not independent factors for recurrence, on multivariate logistic regression analysis ER and PR as continuous values showed recurrence associated with greater ER expression (p = 0.0836) and lesser PR expression (p = 0.0986). Cox proportional hazards model supported the association between increasing ER and decreasing PR with shorter recurrence free survival (p=0.0034, p = 0.0021). An increase in ER score of 1 corresponded to a hazard ratio (HR) of 2.647 (95% CI 1.38-5.08); an increase in PR score of 1 corresponded to a HR of 0.362 (0.19-0.693). Conclusions: More than 50% of high-risk endometrial cancers in this small retrospective cohort receiving cytotoxic chemotherapy expressed positive hormone receptors. Multivariate analyses of hormone receptors suggest increased recurrence with discordant expression of ER and PR. Further investigation is warranted to verify whether differential hormone receptor expression predicts poorer response to cytotoxic systemic therapy.

Molecular markers and clinical behavior of uterine carcinosarcomas: focus on the epithelial tumor component

Carcinosarcomas (malignant mixed Müllerian tumors) of the uterus are rare and aggressive malignancies consisting of an epithelial (carcinoma) and a mesenchymal (sarcoma) tumor component and are considered as metaplastic endometrial carcinomas. This study evaluated molecular characteristics and clinical behavior of uterine carcinosarcomas to improve treatment regimens in the future. Immunohistochemical expression of estrogen receptor-α and -β, progesterone receptor-A and -B, MLH1, MSH2, MSH6, PTEN (phosphatase and tensin homolog deleted on chromosome 10), p53, β-catenin and cyclin D1 was determined in 40 uterine carcinosarcomas. Immunostaining was compared between epithelial and mesenchymal tumor components. To determine the prognostic role of the epithelial component, clinicopathological data and survival were compared between patients with endometrioid and non-endometrioid epithelial tumor components. To determine prognosis of carcinosarcomas compared with high-risk endometrial carcinomas, clinicopathological characteristics and survival were compared between these patients. Hormone receptor expression occurred infrequently: estrogen receptor-α (8%) and -β (32%), progesterone receptor-A (0%) and -B (23%), next to β-catenin (4%) and cyclin D1 (7%). PTEN, MLH1, MSH2 and MSH6 mutations occurred in 39%, 33%, 22% and 21%, respectively (based on absent immunostaining). Overexpression of p53 was observed in 38%. Expression patterns of p53, MSH2 and MSH6 corresponded between epithelial and mesenchymal tumor components. In our cohort, the epithelial component caused the majority of metastases (72%) and vascular invasion (70%). Survival tended to be worse for patients with a non-endometrioid epithelial component compared with an endometrioid epithelial component (5-year survival: 26% and 55%, respectively). Survival was worse for patients with uterine carcinosarcomas compared with high-risk endometrial carcinomas (grade 3 endometrioid and non-endometrioid); 5-year survival rates: 42%, 77% and 57%, respectively. Our results support the monoclonal origin of uterine carcinosarcomas. The epithelial component determines prognosis by causing the majority of metastases and vascular invasion. To improve prognosis, treatment should focus on the epithelial tumor component of uterine carcinosarcomas.

159 TGF-β1 as a therapeutic target in high risk endometrial carcinomas

159 TGF-β1 as a therapeutic target in high risk endometrial carcinomas

Adjuvant treatment with concomitant radiotherapy and chemotherapy in high-risk endometrial cancer: A clinical experience

Objective The concurrent use of radiotherapy (RT) and chemotherapy (CT) as adjuvant treatment after surgery in high-risk endometrial cancer has been generally considered cautiously. Recently some of us have reported preliminary data on the efficacy and tolerability of concomitant CT and RT. In this paper, we update our experience. Methods A total of 47 patients aged > 18 years and < 80 years with histological diagnosis of high-risk endometrial endometrioid carcinomas entered the study. Inclusion criteria were stages IC G3, IIB, IIIA (patients with positive washing without other unfavourable prognostic factors were omitted), IIIB and IIIC. The radiation plan consisted of a total dose of 50.4 Gy, given in five fractions per week (1.8 Gy: daily dose) for 6 weeks. Paclitaxel (P) at a dose of 60 mg/m 2 was infused intravenously in 250 mL of normal saline for 1 h once weekly during RT for 5 weeks. Three further cycles of Paclitaxel, at a dose of 80 mg/m 2, have been given weekly at the end of RT. Results There was no life-threatening toxicity. The overall 5-year relapse-free survival was 81.8% (95% CI, 65.2–90.9). The 5-year percent overall disease-specific survival was 88.4% (95% CI, 71.1–95.6). Conclusions These results, based on a larger series, support our previous data: Paclitaxel plus RT may represent an effective and well-tolerated treatment in high-risk endometrial cancer patients.

Similar Prognosis for Papillary Serous, Clear Cell and Grade 3 Endometrioid Endometrial Carcinomas–A Cancer Registry Analysis

Evaluate and compare prognosis of high-risk endometrial carcinomas (HREC)-with different morphologies-papillary serous (PS), clear cell (CC) and grade 3 endometrioId adenocarcinomas (G3) adjusted for tumor, patient and treatment prognostic factors.

Pathologic expression of p53 or p16 in preoperative curettage specimens identifies high-risk endometrial carcinomas

The purpose of this study was to investigate the prognostic impact of p53 and p16 expression in curettage material from patients with endometrial carcinoma. Preoperative curettage material from a population-based series of 236 endometrial carcinomas from Norway with long and complete follow-up was studied immunohistochemically for p53 and p16 expression. Pathologic expression of p53 and p16 was seen in 24% and 25%, respectively, and was significantly correlated with high International Federation of Gynecology and Obstetrics (FIGO) stage and serous/clear cell histologic subtypes. Pathologic p53 expression showed significant correlation with postmenopausal status, high grade, high tumor cell proliferation, and aneuploidy. Patients with normal expression had 85% 5-year survival compared with 51% and 50% when pathologic expression of p53 and p16, respectively. Five-year survival for patients with 2 pathologic markers was 13%, compared with 67% and 91% for 1 or no pathologic markers, respectively. Pathologic expression of p53 and p16 in curettage material identifies high-risk endometrial carcinoma patients with poor prognosis.