Low-grade and early-stage endometrioid endometrial carcinomas (EECs) have an overall good prognosis but biomarkers identifying patients at risk of relapse are still lacking. Recently, CTNNB1 exon 3 mutation has been identified as a potential risk factor of recurrence in these patients. We evaluate the prognostic value of CTNNB1 mutation in a single-centre cohort of 218 low-grade, early-stage EECs, and the correlation with beta-catenin and LEF1 immunohistochemistry as candidate surrogate markers. CTNNB1 exon 3 hotspot mutations were evaluated by Sanger sequencing. Immunohistochemical staining of mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6), p53, beta-catenin, and LEF1 was performed in representative tissue microarrays. Tumours were also reviewed for mucinous and squamous differentiation, and MELF pattern. Nineteen (8.7%) tumours harboured a mutation in CTNNB1 exon 3. Nuclear beta-catenin and LEF1 were significantly associated with CTNNB1 mutation, showing nuclear beta-catenin a better specificity and positive predictive value for CTNNB1 mutation. Tumours with CTNNB1 exon 3 mutation were associated with reduced disease-free survival (p = 0.010), but no impact on overall survival was found (p = 0.807). The risk of relapse in tumours with CTNNB1 exon 3 mutation was independent of FIGO stage, tumour grade, mismatch repair protein expression, or the presence of lymphovascular space invasion. CTNNB1 exon 3 mutation has a negative impact on disease-free survival in low-grade, early-stage EECs. Nuclear beta-catenin shows a higher positive predictive value than LEF1 for CTNNB1 exon 3 mutation in these tumours. Graphical abstract

In cancer patients, psychological distress, which encompasses anxiety, depression, and somatization, arises from the complex interplay of emotional and behavioral reactions to the diagnosis and treatment, significantly influencing their functionality and quality of life. The aim was to investigate factors associated with psychological distress in cancer patients. This prospective and multicenter study, conducted by the Spanish Society of Medical Oncology (SEOM), included two cohorts of patients with cancer (localized resected or advanced unresectable). They completed surveys assessing psychological distress (BSI-18) before and after cancer treatment and coping (MINI-MAC) and spirituality (FACIT-sp) prior to therapy. A multivariable logistic regression analysis and a Structural Equation Modeling (SEM) were conducted. Between 2019 and 2022, 1807 patients were evaluated, mostly women (54%), average age 64 years. The most frequent cancers were colorectal (30%), breast (25%) and lung (18%). Men had lower levels of anxiety and depression (OR 0.66, 95% CI 0.52–0.84; OR 0.72, 95% CI 0.56–0.93). Colorectal cancer patients experienced less anxiety (OR 0.63, 95% CI 0.43–0.92), depression (OR 0.55, 95% CI 0.37–0.81), and somatization (OR 0.59, 95% CI 0.42–0.83). Patients with localized cancer and spiritual beliefs had reduced psychological distress, whereas those with anxious preoccupation had higher level. SEM revealed a relationship between psychological distress and coping strategies, emphasizing how baseline anxious preoccupation exacerbates post-treatment distress. This study suggests that age, sex, extension and location of cancer, coping and spirituality influence psychological distress in cancer patients.

Objectives Cancer-related systemic inflammation has been associated with prognosis in multiple cancer types. Conversely, local inflammation, which is characterized by dense intratumoral immune infiltrates, is a favorable predictor of survival outcome. However, these survival associations are not well established in ovarian cancer, particularly in the less frequent endometrioid and clear cell endometriosis associated histotypes. Methods This retrospective study included 119 patients (63 endometrioid and 56 clear cell ovarian carcinomas). We performed a comprehensive survival association analysis of both systemic (neutrophil-to-lymphocyte ratio or presence of endometriosis) and local inflammation markers (CD3+ and CD8+ tumor infiltrating lymphocytes) using multivariate Cox proportional hazards models that account for confounding factors. Results Medium to high levels of intraepithelial CD8+ tumor infiltrating lymphocytes are associated with longer survival in endometrioid ovarian cancer (p=0.04). In addition, we found that intraepithelial CD8+ tumor infiltrating lymphocytes are prognostic in clear cell ovarian cancer (p=0.02), and that intraepithelial CD3+ tumor infiltrating lymphocytes are also associated with improved outcome (p=0.02). Furthermore, intratumoral CD3+ and CD8+ tumor infiltrating lymphocytes showed improved prognosis in the endometrioid subtype (p<0.1). No prognostic value was observed for systemic immune markers. Conclusions In this study, patients with endometrioid and clear cell ovarian cancer with moderate to high CD8+ and CD3+ intraepithelial tumor infiltrating lymphocytes had longer overall survival. Higher expression of intratumoral CD3+ and CD8+ tumor infiltrating lymphocytes also showed an improved outcome in endometrioid ovarian cancer. In contrast, systemic inflammation, evaluated by neutrophil-to-lymphocyte ratio or presence of endometriosis, did not have a prognostic impact in these histologic subtypes.

Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. Although most cases are diagnosed at an early stage, prognosis in case of relapse or metastasis remains poor. Molecular characterization of EC is highly recommended as it allows more accurate risk stratification and may modify treatment recommendations. The updated FIGO 2023 staging of EC highlights the importance of traditional clinicopathological factors, while underlining the need for molecular classification to predict outcomes. In early-stage EC, standard treatment consists of total hysterectomy and bilateral salpingo-oophorectomy. Lymph node evaluation remains controversial, as the benefits of systematic lymphadenectomy are unclear. Adjuvant treatment, consisting of radiotherapy, brachytherapy, and chemotherapy, should be chosen according to risk category. In women with advanced or recurrent EC, the combination of carboplatin and paclitaxel has long been standard treatment. However, therapeutic options have changed recently due to advances in immunotherapy. The aim of this guideline is to summarize the current evidence for the diagnosis, treatment, and follow-up of EC, and to provide evidence-based recommendations for clinical practice.