Emine Kilic Bagir

Prognostic Significance of Immune Checkpoint Markers in Prognosis of Grade 3 Endometrioid Carcinoma

Background and Objectives: Uterine FIGO grade 3 endometrioid carcinoma (EC) is an uncommon but aggressive subtype of endometrial cancer with limited biomarker data to guide prognosis and management. This study aimed to evaluate the prognostic significance of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) expression in tumor tissue (TT) and tumor microenvironment (TME). Materials and Methods: We retrospectively analyzed tumor samples from 53 patients with FIGO grade 3 EC. Immunohistochemistry was performed to assess PD-1 and PD-L1 expression in TT and TME. Clinicopathological data including age, stage, lymph node invasion (LNI), lymphovascular space invasion (LVSI), depth of myometrial invasion (MI), adjuvant therapy, and survival outcomes were collected. Survival analyses were conducted using Kaplan–Meier and Cox proportional hazards models. Results: PD-1 expression was identified in 34% of TT and 41.5% of TME, while PD-L1 was expressed in 22.6% of TT and 34% of TME. Except for PD-1 in TME, positive expression of these immune checkpoint molecules correlated with significantly shorter survival (log-rank p < 0.05) outcomes. In univariate analysis, PD-1 and PD-L1 expression in TT, deep MI, LNI and LVSI were associated with adverse outcomes. Multivariate analysis confirmed PD-1 and PD-L1 positivity in TT as independent prognostic factors (PD-1: HR 3.2, 95% CI 1.4–7.0; PD-L1: HR 3.3, 95% CI 1.4–7.8). Patients with concurrent PD-1 and PD-L1 expression in TT showed the poorest overall survival, suggesting a cumulative negative effect. Conclusions: PD-1 and PD-L1 expression in tumor tissue are independent predictors of poor prognosis in FIGO grade 3 EC. These findings support their role as clinically relevant biomarkers and potential therapeutic targets. Incorporating checkpoint evaluation into routine pathological assessment could improve prognostic accuracy and guide treatment strategies, particularly in high-risk patients who might benefit from immunotherapy approaches.

Clinicopathologic characteristics and prognosis comparison of the uterine high grade endometrial carcinomas

Grade 3 endometrioid adenocarcinomas (G3 EAC), type two endometrial carcinomas (Type 2 EC), and also uterine carcinosarcomas (UCS) are considered as high-grade endometrial adenocarcinomas. The aim of this study was to compare the clinicopathologic features and survival of patients with UCS, G3 EAC, Type2 EC. We included two hundred and thirty-five patients in this study. Patients were divided into three groups according to the type of tumor as uterine G3 EAC (group 1, n = 62), Type 2 EC (serous, clear and mixed types; group 2, n = 93), and UCS (group 3, n = 80). We compared the groups according to age, initial symptom, surgical approach, stage, myometrial invasion (MI), lymph node invasion (LNI), lymphovascular space invasion (LVSI), adjuvant therapy, and survival. When comparing the survival outcomes the Kaplan-Meier analysis was performed. The groups were similar according to age, menopausal status, nulliparity, initial symptoms, stage, LVSI, and LNI. Positive cytology was determined significantly more in group 3. There was a significant difference between the groups in terms of myometrial invasion degree. Optimal cytoreduction was similar among the groups. The primary adjuvant treatment was chemotherapy for UCS and Type2 EAC whereas radiotherapy was the main adjuvant treatment for G3 EAC. There were no significant differences among the groups according to overall survival (OS) (p = 0.290). Although the survival difference among the groups can not be revealed, these patients have different clinical and pathological features and they should be considered as different groups.

Prognosis Trend of Grade 2 Endometrioid Endometrial Carcinoma: Toward Grade 1 or 3?

Although the prognostic significance of grade in endometrial cancer is well known, grade 2 cases have not been evaluated separately in most of the previous studies. In this study, we aim to investigate whether the oncologic outcomes of grade 2 endometrioid endometrial carcinomas trend towards grade 1 or 3 tumors. Patients' records and pathological reports were reviewed retrospectively and eligible patients with endometrioid endometrial carcinoma were determined and distributed into 3 groups according to their 1988 International Federation of Gynecology and Obstetrics (FIGO) grade. Groups' characteristics and oncologic outcomes were compared. Differences between grades were tested with z-test and adjusted by Bonferroni method. Kaplan-Meier method was performed for the survival analysis. In total, 776 patients of endometrioid endometrial carcinoma were included in this study. Mean follow-up time was 52 ± 14 months. Patients' mean age was 56.3 ± 10.8 years. Even though grade 2 endometrioid endometrial carcinomas were different from both grade 1 and 3 in terms of the pathological features, survival analyses demonstrated that their oncologic outcomes trended towards grade 1. The grade was determined as an independent prognostic factor for overall survival (OS). The interobserver reproducibility will be improved among pathologists by combining FIGO grade 1 and 2 endometrioid endometrial carcinomas, while prognosis prediction is not likely to be affected.