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Simple Summary: Oestrogen and progesterone are two sex hormones that are important in the development of cancer of the inner lining of the uterus and endometrial cancer (EC). Oestrogen binds to the oestrogen receptor (ER) and progesterone to the progesterone receptor (PR). The presence of these receptors is important because the response to hormonal therapy is higher when the receptors are present. However, as EC grows and spreads throughout the body, ER and PR may be lost. In this study, we found that tumours that have spread to other organs throughout the blood and tumours that have spread in the abdomen have a relatively high presence of ER/PR, while tumours located in the lymph nodes have a lower presence of PR. ER/PR-IHC were not lower in tumours that had previously been treated with radiotherapy. This might influence the application of hormonal therapy in the future. Background: Response to hormonal therapy in advanced and recurrent endometrial cancer (EC) can be predicted by oestrogen and progesterone receptor immunohistochemical (ER/PR-IHC) expression, with response rates of 60% in PR-IHC > 50% cases. ER/PR-IHC can vary by tumour location and is frequently lost with tumour progression. Therefore, we explored the relationship between ER/PR-IHC expression and tumour location in EC. Methods: Pre-treatment tumour biopsies from 6 different sites of 80 cases treated with hormonal therapy were analysed for ER/PR-IHC expression and classified into categories 0–10%, 10–50%, and >50%. The ER pathway activity score (ERPAS) was determined based on mRNA levels of ER-related target genes, reflecting the actual activity of the ER receptor. Results: There was a trend towards lower PR-IHC (33% had PR > 50%) and ERPAS (27% had ERPAS > 15) in lymphogenic metastases compared to other locations (p = 0.074). Hematogenous and intra-abdominal metastases appeared to have high ER/PR-IHC and ERPAS (85% and 89% ER-IHC > 50%; 64% and 78% PR-IHC > 50%; 60% and 71% ERPAS > 15, not significant). Tumour grade and previous radiotherapy did not affect ER/PR-IHC or ERPAS. Conclusions: A trend towards lower PR-IHC and ERPAS was observed in lymphogenic sites. Verification in larger cohorts is needed to confirm these findings, which may have implications for the use of hormonal therapy in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with high-grade uterine cancer (UC) have a risk of around 20% of the cancer spreading to the lymph nodes, while this is only around 10% in patients with low-grade uterine cancer. CA125 is a marker that can be detected in blood and is associated with increased tumor spread. Studies on CA125 and its association with tumor spread within low-grade UC exist but are limited for high-grade UC. The primary aim of this retrospective study was to assess whether elevated CA125 is predictive for UC spread and survival. Secondarily, we studied the additional value of preoperative imaging by CT scan in relation to CA125 specifically in high-grade UC. We observed that elevated CA125 was related to advanced stage and LNM in high-grade UC and a worse prognosis. If CA125 was normal, the additional value of CT to predict lymph node spread was limited. Patients with high-grade endometrial carcinoma (EC) have an increased risk of tumor spread and lymph node metastasis (LNM). Preoperative imaging and CA125 can be used in work-up. As data on cancer antigen 125 (CA125) in high-grade EC are limited, we aimed to study primarily the predictive value of CA125, and secondarily the contributive value of computed tomography (CT) for advanced stage and LNM. Patients with high-grade EC (n = 333) and available preoperative CA125 were included retrospectively. The association of CA125 and CT findings with LNM was analyzed by logistic regression. Elevated CA125 ((>35 U/mL), (35.2% (68/193)) was significantly associated with stage III-IV disease (60.3% (41/68)) compared with normal CA125 (20.8% (26/125), [p < 0.001]), and with reduced disease-specific—(DSS) (p < 0.001) and overall survival (OS) (p < 0.001). The overall accuracy of predicting LNM by CT resulted in an area under the curve (AUC) of 0.623 (p < 0.001) independent of CA125. Stratification by CA125 resulted in an AUC of 0.484 (normal), and 0.660 (elevated). In multivariate analysis elevated CA125, non-endometrioid histology, pathological deep myometrial invasion ≥50%, and cervical involvement were significant predictors of LNM, whereas suspected LNM on CT was not. This shows that elevated CA125 is a relevant independent predictor of advanced stage and outcome specifically in high-grade EC. [ABSTRACT FROM AUTHOR]