Rationale: The ProMisE molecular classification improves risk assessment in endometrial cancer (EC), but 3–11% of cases exhibit overlapping molecular features, complicating clinical decisions. We analyzed the prevalence and clinicopathological profiles of multiple-classifier ECs in a large Polish cohort. Methods: In this retrospective study (2022–2025), 1075 ECs from four institutions were classified by MMR and p53 immunohistochemistry and POLE exon sequencing. Tumors showing ≥2 molecular features (e.g., MMRd–p53abn, POLEmut–p53abn) were categorized as multiple-classifier ECs. Results: Multiple-classifier ECs comprised 6.9% (74/1075), with MMRd–p53abn (3.9%) being most common. These tumors exhibited more aggressive features vs. MMRd-only: G3 (28.57% vs. 11.79%, p = 0.002), non-endometrioid histology (11.9% vs. 2.85%, p = 0.018), and high–intermediate/high-risk (HIR/HR) groups (59.52% vs. 37.80%, p = 0.001). POLEmut–p53abn (N = 4) and POLEmut–MMRd–p53abn (N = 10) tumors showed advanced stages (75% and 40% FIGO III–IV, respectively), in contrast to classical POLEmut tumors (6.7% FIGO III–IV), and higher rates of nodal metastases. Conclusions: Co-occurrence of molecular classifiers, including triple-classifier tumors, correlates with more adverse profiles and may undermine current stratification paradigms. This study emphasizes the need to further investigate and refine molecular risk models to account for overlapping profiles.

Background: Endometrial cancer (EC) incidence and mortality have been steadily rising globally over recent decades. The introduction of advanced molecular technologies, such as next-generation sequencing (NGS) alongside the FIGO 2023 classification, presents opportunities for refined diagnostics and risk stratification. This study aimed to analyze differences in EC classification among oncology centers in southeastern Poland. Methods: Data were collected from 461 consecutive patients newly diagnosed with EC between 2022 and 2024 at four major oncology centers in southeastern Poland. Molecular and immunohistochemical (IHC) analyses were conducted on formalin-fixed paraffin-embedded (FFPE) tissues to identify key markers, including POLE mutations, MSI-H, and p53 status. Results: The application of the FIGO 2023 staging system revealed statistically significant inter-center differences, with Centers 1 and 4 diagnosing a higher proportion of early-stage cases. The most prevalent subtype was NSMP, observed in 51% of cases. MSI-H occurred in 13–36% of patients, depending on the center. p53 mutations ranged from 9% to 26%. POLE mutations were identified in 4% of patients overall. Significant variations in the molecular subtype distribution across centers highlight potential differences in diagnostic access or tumor biology. Conclusions: The findings demonstrate regional differences in EC staging and molecular profiles in Poland, potentially reflecting disparities in diagnostic resources, methodologies, or tumor characteristics. Addressing these variations through standardized diagnostic protocols and equitable access to molecular tools is critical for optimizing patient outcomes. Future research should focus on evaluating the impact of molecular markers on therapy response and prognosis to guide personalized treatment strategies.

Sentinel lymph node (SLN) identification plays a crucial role in the diagnosis and management of gynecological cancers, particularly in the context of lymph node metastases that often remain undetectable through standard imaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET). Therefore, surgical assessment of lymph nodes remains an essential component of diagnostic procedures. SLN biopsy enables the detection of small metastatic deposits while reducing the need for extensive lymphadenectomy and minimizing associated complications. Lymphoscintigraphy using technetium-99m (Tc-99m) is one of the most commonly applied techniques for lymphatic mapping and is considered the standard method for SLN identification. In clinical practice, Tc-99m is frequently combined with indocyanine green (ICG) or methylene blue (MB) to allow dual visualization. The dye method, despite its simplicity, has certain limitations, such as shorter retention time in lymph nodes and the risk of diffusion into capillaries, which may reduce detection efficiency. Lymphoscintigraphy with Tc-99m provides precise visualization of lymphatic drainage pathways and SLNs, contributing to a more accurate determination of cancer staging and reducing the number of unnecessary lymphadenectomies. The appropriate application of this technique lowers the risk of complications, such as lymphedema, while maintaining high diagnostic accuracy. This review summarizes current evidence on the clinical application of Tc-99m in SLN detection for gynecological cancers, analyzing both its advantages and the challenges related to its practical implementation. Additionally, it discusses the technical aspects of Tc-99m use and its role as a reliable tool for optimizing oncological outcomes. Keywords: technetium-99m sentinel lymph node gynecological cancer

Background/Objectives: The preoperative detection of sentinel lymph nodes (SLN) using technetium-99m (Tc-99m) is crucial for surgical staging in early-stage endometrial cancer (EC). The optimal imaging timing and modality remain debated. This study compares early planar scintigraphy (30 min), SPECT/CT (1 h), and 18-h planar scintigraphy after a single Tc-99m injection. Methods: A total of 125 patients with early-stage EC underwent SLN mapping with Tc-99m (120 MBq). Imaging included 30-min planar scintigraphy, SPECT/CT (1 h), and 18-h planar scintigraphy on the day of surgery. Detection sensitivity, the bilateral mapping rate, and image quality (signal-to-noise ratio (SNR), contrast factor (C-factor)) were evaluated, with intraoperative gamma probe detection and histopathology as references. Results: The 18-h planar scintigraphy achieved the highest SLN detection sensitivity (94.4%, 118/125), compared with SPECT/CT (87.2%, OR = 2.48, 95% CI: 0.98–6.27, p = 0.051) and 30-min scintigraphy (72.0%). Only the 18-h protocol underwent intraoperative and histopathological verification; results for 30-min planar and 1-h SPECT/CT were based on imaging alone, which limits direct comparability. Bilateral detection was higher at 18 h (80.80%) than SPECT/CT (73.60%). All SLNs detected at 18 h were confirmed intraoperatively and histologically, yielding 100% PPV (95% CI: 96.9–100.0%) and NPV (95% CI: 59.0–100.0%). The 18-h protocol showed superior imaging contrast (C-factor: 10.30 ± 1.22) despite lower residual activity. The method remained effective in patients with BMI ≥ 30 (94.00%). Only 1.60% of patients required hysterectomy before mapping due to background interference. Conclusions: The 18-h planar scintigraphy is a highly effective, low-cost, and accessible method for SLN detection in early-stage EC, potentially reducing the need for SPECT/CT, radiation exposure, and costs.

Rationale: The ProMisE molecular classification improves risk assessment in endome-trial cancer (EC), but 3–11% of cases exhibit overlapping molecular features, compli-cating clinical decisions. We analyzed the prevalence and clinicopathological profiles of multiple-classifier ECs in a large Polish cohort. Methods: In this retrospective study (2022–2025), 1075 ECs from four institutions were classified by MMR and p53 immunohistochemistry and POLE exon sequencing. Tumors showing ≥2 molecular features (e.g., MMRd–p53abn, POLEmut–p53abn) were categorized as multiple-classifier ECs. Results: Multiple-classifier ECs comprised 6.9% (74/1075), with MMRd–p53abn (3.9%) being most common. These tumors exhibited more aggressive features vs MMRd-only: G3 (28.57% vs 11.79%, p=0.002), non-endometrioid histology (11.9% vs 2.85%, p=0.018), and higher-risk stratification (59.52% vs 37.80%, p=0.001). POLEmut–p53abn (N=4) and POLEmut–MMRd–p53abn (N=10) tumors showed advanced stages (75% and 40% FIGO III–IV, respectively), in contrast to classical POLEmut tumors (6.7% FIGO III–IV), and higher rates of nodal metastases. Conclusion: Co-occurrence of molecular classifiers, including triple-classifier tumors, correlates with more adverse profiles and may undermine current stratification para-digms. This study emphasizes the need to further investigate and refine molecular risk models to account for overlapping profiles.

To determine how often lymph node assessment alters post-operative risk classification or adjuvant therapy in p53-abnormal endometrial carcinoma and to calculate the number needed to stage to obtain 1 management-changing result. This multicenter retrospective study included patients with biopsy-confirmed p53-abnormal endometrial carcinoma who underwent pre-operative expert ultrasound, molecular classification, and definitive surgery. Pre-operative risk groups were based on ultrasound-assessed invasion and molecular subtype; post-operative groups incorporated final pathology and lymph node status. The number needed to stage was defined as the number of patients staged divided by the number with management-changing results. Among 120 patients, lymph node status was evaluable in 107, with metastases identified in 19 (17.8%) cases. Concordance between pre-operative and post-operative risk groups was 84.2%. Reclassification occurred in 15.8% of patients and was driven entirely by uterine pathological findings. Lymph node findings altered guideline-based post-operative management in only 2 of 107 patients (1.9%; 95% confidence interval 0.2% to 6.6%), both through treatment de-escalation based on negative nodal status. No escalation of adjuvant therapy was triggered by nodal metastases. The number needed to stage was 53.5. In this multicenter cohort of p53-abnormal endometrial carcinoma, lymph node assessment had a limited impact on guideline-based post-operative management, with treatment decisions largely driven by molecular subtype and uterine pathological factors. Prospective, molecularly stratified studies are needed to clarify the optimal role of nodal staging in this patient population.