Aneuploidy related transcriptional changes in endometrial cancer link low expression of chromosome 15q genes to poor survival.

Aneuploidy is a widely studied prognostic marker in endometrial cancer (EC), however, not implemented in clinical decision-making. It lacks validation in large prospective patient cohorts adjusted for currently standard applied prognostic markers, including estrogen/progesterone receptor status (ER/PR). Also, little is known about aneuploidy-related transcriptional alterations, relevant for understanding its role in EC biology, and as therapeutic target.We included 825 EC patients with available ploidy status and comprehensive clinicopathologic characterization to analyze ploidy as a prognostic marker. For 144 patients, gene expression data were available to explore aneuploidy-related transcriptional alterations.Aneuploidy was associated with high age, FIGO stage and grade, non-endometrioid histology, ER/PR negativity, and poor survival (p-values<0.001). In patients with ER/PR negative tumors, aneuploidy independently predicted poor survival (p=0.03), lymph node metastasis (p=0.007) and recurrence (p=0.002). A prognostic 'aneuploidy signature', linked to low expression of chromosome 15q genes, was identified and validated in TCGA data.In conclusion, aneuploidy adds prognostic information in ER/PR negative EC, identifying high-risk patients that could benefit from more aggressive therapies. The 'aneuploidy signature' equally identifies these aggressive tumors and suggests a link between aneuploidy and low expression of 15q genes. Integrated analyses point at various dysregulated pathways in aneuploid EC, underlining a complex biology.

High Diagnostic Value of 18F-FDG PET/CT in Endometrial Cancer: Systematic Review and Meta-Analysis of the Literature.

UNLABELLED: The aim of this study was to evaluate the diagnostic performance of (18)F-FDG PET/CT for the preoperative assessment of lymph node metastases (LNM) in endometrial cancer patients and for the assessment of endometrial cancer recurrence (ECR) after primary surgical treatment. METHODS: A comprehensive search was performed on Pubmed/MEDLINE databases for studies reporting the diagnostic performance of (18)F-FDG PET/CT for assessment of LNM and ECR published up to August 15, 2015. Twenty-one studies (13 for LNM and 8 for ECR) were included in the systematic review and meta-analysis. Pooled estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of the (18)F-FDG PET/CT were calculated along with 95% confidence intervals (CIs). A summary receiver-operating-characteristics curve (SROC) was constructed, and the area under the SROC curve (AUC) was determined along with Q* index. RESULTS: The overall pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and AUC (with 95% CI) of (18)F-FDG PET/CT for detection of LNM were 0.72 (95% CI, 0.63-0.80), 0.94 (95% CI, 0.93-0.96), 10.9 (95% CI, 7.9-15.1), 0.36 (95% CI, 0.27-0.48), 39.7 (95% CI, 21.4-73.6), and 0.94 (95% CI, 0.85-0.99), respectively, whereas the corresponding numbers for detection of ECR were 0.95 (95% CI, 0.91-0.98), 0.91 (95% CI, 0.86-0.94), 8.8 (95% CI, 6.0-12.7), 0.08 (95% CI, 0.05-0.15), 171.7 (95% CI, 67.9-434.3), and 0.97 (95% CI, 0.95-0.98), respectively. The overall diagnostic accuracy (Q* index) in LNM and ECR were 0.88 and 0.93, respectively. CONCLUSION: (18)F-FDG PET/CT has an excellent diagnostic performance for detecting LNM preoperatively and disease recurrence postoperatively in endometrial cancer patients.

Clinical value of dna content assessment in endometrial cancer.

Endometrial carcinoma (EC) is the most common gynecologic cancer in industrialized countries. Traditional prognostic markers include FIGO stage, histologic subtype and histologic grade. DNA ploidy was introduced as a prognostic marker 30 years ago, and the majority of published literature demonstrates significant associations between tumor aneuploidy and poorer prognosis in EC. However, ploidy analysis is not routinely implemented in the clinic. We reviewed the literature on clinical value of ploidy measured by DNA content as a prognostic marker, and its potential role as a predictive marker in EC. PubMed was searched for papers evaluating the prognostic or predictive role of ploidy in EC. Search criteria were "DNA ploidy prognosis/predictive value endometrial cancer/carcinoma". Only articles written in English, published year 2000 or later were included. The majority of the studies demonstrated highly significant correlation between DNA index (DI) and survival, in univariate analysis including stages I-IV, and in subgroup analysis of stage I and stage I-II EC. Several studies also showed significant association between DI and survival in multivariate analysis. Few studies have evaluated DI as a prognostic marker in a prospective setting. No studies evaluating DI as a predictive marker in EC were identified. In other cancer types, ploidy has been linked to prediction of response to hormonal therapy and chemotherapy. Ploidy assessment in EC by DI is a strong prognostic marker. Still, its clinical applicability needs validation in a routine diagnostic, prospective setting with sufficient number of patients, characterized by state of the art histopathological evaluation and surgical staging. © 2014 Clinical Cytometry Society.

Clinical value of DNA content assessment in endometrial cancer.

Endometrial carcinoma (EC) is the most common gynecologic cancer in industrialized countries. Traditional prognostic markers include FIGO stage, histologic subtype, and histologic grade. DNA ploidy was introduced as a prognostic marker 30 years ago, and the majority of published literature demonstrates significant associations between tumor aneuploidy and poorer prognosis in EC. However, ploidy analysis is not routinely implemented in the clinic. We reviewed the literature on clinical value of ploidy measured by DNA content as a prognostic marker, and its potential role as a predictive marker in EC. PubMed was searched for papers evaluating the prognostic or predictive role of ploidy in EC. Search criteria were "DNA ploidy prognosis/predictive value endometrial cancer/carcinoma". Only articles written in English, published year 2000 or later were included. The majority of the studies demonstrated highly significant correlation between DNA index (DI) and survival, in univariate analysis including stages I-IV, and in subgroup analysis of stage I and stage I-II EC. Several studies also showed significant association between DI and survival in multivariate analysis. Few studies have evaluated DI as a prognostic marker in a prospective setting. No studies evaluating DI as a predictive marker in EC were identified. In other cancer types, ploidy has been linked to prediction of response to hormonal therapy and chemotherapy. Ploidy assessment in EC by DI is a strong prognostic marker. Still, its clinical applicability needs validation in a routine diagnostic, prospective setting with sufficient number of patients, characterized by state of the art histopathological evaluation and surgical staging.

Growth differentiation factor-15 as biomarker in uterine sarcomas.

OBJECTIVE: The aim of this study was to investigate and validate circulating growth differentiation factor-15 (GDF-15) as a discriminating biomarker between highly malignant uterine sarcomas and benign uterine leiomyomas. In addition, we investigated whether GDF-15 differed between uterine sarcomas and benign adnexal tumors, ovarian or endometrial cancer, and borderline tumors of the ovary. MATERIALS AND METHODS: Preoperative blood samples from 19 women with a diagnosis of uterine sarcoma were analyzed for GDF-15 with immunoassay and compared with samples from 50 patients operated on for leiomyoma uteri and with samples from 20 premenopausal and 20 postmenopausal controls. Our previously presented preoperative GDF-15 concentrations in women with borderline (n = 43), benign (n = 144), and malignant ovarian tumors (n = 125), as well as endometrial cancer (n = 510), were used for comparison. RESULTS: The median circulating GDF-15 concentration was elevated in the uterine sarcoma group (943 ng/L) compared with the myoma uteri group (647 ng/L), the premenopausal and postmenopausal controls (363 and 545 ng/L), and the women with benign ovarian tumors (591 ng/L, all P ≤ 0.007) but was not significantly different from the ovarian borderline tumor (718 ng/L) or ovarian (1242 ng/L) or endometrial cancer (1076 ng/L) groups.High GDF-15 levels were significantly associated with leiomyosarcomas (P = 0.036), advanced disease (International Federation of Gynecology and Obstetrics stage III/IV, P = 0.013), large tumors (≥10 cm, P = 0.009), and poor survival (P = 0.022). CONCLUSIONS: Circulating GDF-15 may be a promising novel biomarker for the preoperative identification of malignant pelvic disease. Further large prospective studies are needed to evaluate the clinical usefulness of GDF-15 as a discriminator between benign leiomyomas and aggressive sarcomas and as a marker to guide surgical and systemic therapy.