Search Results (322)

Background/Objectives: The 2019 WHO classification redefined high-grade gastrointestinal neuroendocrine neoplasms (GI NENs), encompassing not only poorly differentiated neuroendocrine carcinomas (NECs), but also well-differentiated grade 3 neuroendocrine tumors (NETs G3). Since both subtypes share a Ki-67 index > 20%, distinguishing them based solely on morphology is challenging. Prior studies have shown TP53 alterations in NECs but not in NETs. This study aimed to evaluate clinico-morphological parameters and the immunohistochemical (IHC) expression of p53 in high-grade GI NENs to identify relevant correlations. Methods: Tumors were stratified by Ki-67 index into two groups: >20–50% and >50%. p53 IHC expression was assessed as “wild-type” (1–20% positive tumor cells) or “non-wild-type” (absence or >20% positivity). Correlations were analyzed between Ki-67, p53 status, and various pathological features. Results: Significant correlations were found between the Ki-67 index and maximum tumor size, pT stage, lymphovascular invasion, perineural infiltration, and diagnostic classification. Similarly, p53 immunohistochemical status was significantly associated with lymphovascular invasion, lymph node metastasis, and tumor classification (NET G3 versus NEC, including NEC components of MiNENs). Conclusions: The findings support the value of Ki-67 and p53 as complementary biomarkers in the pathological evaluation of high-grade GI NENs. Their significant associations with key morphological parameters support their utility in differentiating NETs G3 from NECs, particularly in cases showing overlapping histological features. The immunohistochemical profile of p53 may serve as a useful diagnostic adjunct in routine practice. Full article

Background/Objectives: The COVID-19 pandemic disrupted global cancer care. This study compared gastric cancer surgical outcomes before and during the pandemic in Turkey. We also aimed to analyze the impact of the pandemic and factors on survival and mortality in gastric cancer patients. Materials and Methods: This retrospective, multicenter cohort study included 324 patients from three tertiary centers in Turkey who underwent gastric cancer surgery between January 2018 and December 2022. Patients were stratified into Pre-COVID-19 (n = 150) and COVID-19 Era (n = 174) groups. Comprehensive demographic, surgical, pathological, and survival data were analyzed. To identify factors independently associated with postoperative mortality, a multivariable logistic regression model was applied. For evaluating predictors of long-term survival, multivariable Cox proportional hazards regression analysis was conducted. Results: The median time from diagnosis to surgery was comparable between groups, while the time from surgery to pathology report was significantly prolonged during the pandemic (p = 0.012). Laparoscopic surgery (p = 0.040) and near-total gastrectomy (p = 0.025) were more frequently performed in the Pre-COVID-19 group. Although survival rates between groups were similar (p = 0.964), follow-up duration was significantly shorter in the COVID-19 Era (p < 0.001). Comparison between survivor and non-survivor groups showed that several variables were significantly associated with mortality, including larger tumor size (p < 0.001), greater number of metastatic lymph nodes (p < 0.001), elevated preoperative CEA (p = 0.001), CA 19-9 (p < 0.001), poor tumor differentiation (p = 0.002), signet ring cell histology (p = 0.003), lymphovascular invasion (p < 0.001), and perineural invasion (p < 0.001). Multivariable logistic regression identified total gastrectomy (OR: 2.14), T4 tumor stage (OR: 2.93), N3 nodal status (OR: 2.87), and lymphovascular invasion (OR: 2.87) as independent predictors of postoperative mortality. Cox regression analysis revealed that combined tumor location (HR: 1.73), total gastrectomy (HR: 1.56), lymphovascular invasion (HR: 2.63), T4 tumor stage (HR: 1.93), N3 nodal status (HR: 1.71), and distant metastasis (HR: 1.74) were independently associated with decreased overall survival. Conclusions: Although gastric cancer surgery continued during the COVID-19 pandemic, some delays in pathology reporting were observed; however, these did not significantly affect the timing of adjuvant therapy or patient outcomes. Importantly, pandemic timing was not identified as an independent risk factor for mortality in multivariable logistic regression analysis, nor for survival in multivariable Cox regression analysis. Instead, tumor burden and aggressiveness—specifically advanced stage, lymphovascular invasion, and total gastrectomy—remained the primary independent determinants of poor prognosis. While pandemic-related workflow delays occurred, institutional adaptability preserved oncologic outcomes. Full article

Background/Objectives: Tumor budding (TB)—clusters of one to five tumor cells at the invasive front—has emerged as a prognostic marker in various cancers. Its prognostic value in head and neck squamous cell carcinoma (HNSCC) is unclear. Methods: We retrospectively analyzed 98 HNSCC patients. The tumor buds were counted on hematoxylin–eosin-stained sections as per the 2016 International Tumor Budding Consensus Conference (ITBCC) guidelines. An optimal cutoff was determined by ROC analysis using excisional lymph nodes and five-year overall survival (OS) as the endpoint, stratifying patients into low- (≤4 buds) and high-risk (>4 buds) groups. The associations with clinicopathological features, OS, and disease-free survival (DFS) were assessed using Kaplan–Meier curves and Cox regression. Results: Among the 98 patients (median follow-up 58 months, range 18–108), 32 (32.7%) died. The optimal TB cutoff was 4.5 (AUC 0.85, 95% CI 0.76–0.93). High TB was associated with poorer five-year OS (26.4% vs. 85.3%). Multivariate Cox regression identified TB and extranodal extension as independent predictors of OS (TB HR: 3.4, 95% CI 1.3–9.2, p = 0.013). In the laryngeal cancer subgroup, TB was associated with worse survival in the univariate analysis (HR 7.5, 95% CI 1.6–35.6, p = 0.011), though this was not significant in the multivariate modeling. High TB independently predicted neck lymph node metastasis (multivariate OR 4.9, 95% CI 1.2–20.5, p = 0.029), which was present in 65.8% of the high-TB vs. 31.7% of the low-TB patients. High TB correlated with advanced AJCC stage and lymphovascular invasion. No clinicopathological factors, including TB, independently predicted DFS, in either the full cohort or the laryngeal subgroup. Conclusions: High tumor budding denotes an aggressive HNSCC phenotype and may guide decisions on elective neck dissection. Its assessment is simple, cost-effective, and potentially valuable for routine pathology, pending external validation. Full article

Colorectal cancer (CRC) diagnosed in an advanced stage has an increased predisposition for invasion and metastasis, requiring upgraded prognostic markers. CDH17, a liver-intestine cadherin, is an adhesion molecule implicated in tumor progression. This retrospective study assessed the immunohistochemical expression of CDH17 in 84 CRC cases with lymphovascular invasion (LVI), analyzing its correlation with clinicopathological features and survival outcomes. CDH17 expression was evaluated in the tumor core, invasive front, tumor emboli, and lymph node metastases. Statistical analyses showed significant associations between high CDH17 expression and favorable histological types, as well as low-grade differentiation. However, high CDH17 levels in tumor emboli correlated with advanced T stage and poorer overall survival. Multivariable Cox regression confirmed CDH17 expression in tumor emboli as an independent prognostic factor, indicating an approximately twofold risk of death. These findings suggest that CDH17 may have a dual role—maintaining adhesion in low-grade tumors while facilitating tumor emboli-related dissemination. CDH17 expression, particularly in the tumor emboli, could serve as a valuable prognostic biomarker in CRC with LVI. Full article

Background/Objectives: Lymphovascular invasion (LVI) has been consistently linked to poor outcomes in patients with bladder cancer (BC), yet its independent prognostic value, especially after adjusting for established pathological features, remains debated. This study aimed to evaluate the prognostic value of LVI in the context of other pathological features of patients undergoing radical cystectomy. Methods: We conducted a retrospective cohort study including 200 patients treated at the Municipal Clinical Hospital in Cluj-Napoca, Romania. Associations between LVI and overall survival (OS) were assessed using univariable and multivariable Cox proportional hazards models, with Kaplan–Meier curves used for visualizing survival distributions. Results: In univariable analysis, increasing age, presence of LVI, advanced pathological tumor stage (pT ≥ 2), and nodal involvement (pN ≥ 1) were significantly associated with worse OS. LVI was a strong predictor of poor survival (HR 3.13; 95% CI: 2.09; 4.69; p < 0.001). However, in multivariable analysis, only tumor stage (HR 4.85; 95% CI: 2.19; 10.77; p < 0.001) and nodal involvement (HR 1.87; 95% CI: 1.13; 3.09; p = 0.015) remained independently associated with OS. In patients with incomplete nodal staging (Nx), LVI was significantly associated with OS (p = 0.028). Conclusions: Our findings reinforce the prognostic relevance of LVI in bladder cancer and support its role as a marker of aggressive tumor biology, highlighting its value in clinical risk assessment, especially in patients with incomplete nodal staging. Routine reporting of LVI in pathology and consideration in treatment planning are warranted. Full article

Background/Objectives: The aim of this study was to investigate the relationship between the PRIMARY score derived from [⁶⁸Ga]Ga-PSMA PET/CT and key clinical and pathological parameters of prostate cancer aggressiveness, including the PSA level, ISUP Grade Group, and D’Amico risk classification, in patients with biopsy-proven prostate cancer. A secondary aim was to evaluate the interobserver agreement of the PRIMARY score in routine clinical practice. Methods: This retrospective analysis included 51 patients with histopathologically confirmed prostate adenocarcinoma who underwent [⁶⁸Ga]Ga-PSMA PET/CT imaging for staging. PRIMARY scores were determined based on the intraprostatic uptake pattern, intensity, and zonal localization. These scores were compared with PSA levels, ISUP GG, D’Amico risk classification, and histopathological features such as the cribriform pattern, intraductal carcinoma, perineural invasion, extraprostatic extension, and lymphovascular invasion. The PRIMARY scores were independently assigned by a total of three nuclear medicine physicians, and interobserver agreement was calculated using Fleiss’ kappa analysis. Results: Significant associations were found between the PRIMARY scores and the PSA level, ISUP Grade Group, and D’Amico risk classification. The most prevalent score was PRIMARY 5 (54.9%), which was significantly associated with ISUP GG 5 and the high-risk category in D’Amico classification. Among patients with PRIMARY Score 2, a substantial proportion (64.7%) had ISUP GG ≥ 3, and 58.8% were in the high-risk group, highlighting the limitations of binary PRIMARY classification. No statistically significant correlations were found between the PRIMARY scores and specific histopathologic features. Interobserver agreement was excellent (κ = 0.833). Conclusions: The PRIMARY score demonstrates high reproducibility and clinical relevance in stratifying prostate cancer aggressiveness. However, the findings challenge the reliability of binary classifications, particularly for patients with Score 2, who may still harbor high-grade disease. Integrating imaging-based scores with clinical and histopathological data is essential, particularly for accurate staging and decision-making regarding active surveillance. Full article

Background/Objectives: Given the increasing interest in the predictive role of inflammation in oncology, we aimed to assess the association between inflammatory factors (IFs) and the histopathological characteristics of bladder cancer (BC). Our objective was to correlate some of these IFs with BC progression and recurrence, identifying possible new diagnostic tools. Methods: We retrospectively analyzed 285 patients (79.8% male, 20.4% female; median age 73) who underwent transurethral resection of the bladder (TURB) between January 2016 and January 2022. The preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), systemic inflammation response index (SIRI), and standard clinical variables were collected one month before TURB and evaluated as predictors of recurrence and progression. Patients were stratified using the Youden Index and ROC analysis. Cox regression models were applied to identify independent predictors. Results: High-grade tumors were present in 74.6% of cases, and 34% were recurrent. Carcinoma in situ was found in 5%. After 72 months, 53% underwent radical cystectomy, and 13.7% died within 5 years. The optimal cutoffs were PLR 139, SIRI 1.12, PIV 248.49, NLR 2, SII 327. Smoking, primary MIBC, age, and lymph node status were significantly associated with recurrence. Elevated PLR correlated with recurrence and T2 progression (p = 0.004). Higher SIRI, PIV, and PLR levels were significantly associated with lymphovascular invasion and nodal metastasis (p < 0.05). PLR was linked to recurrence in tumors ≥ 3 cm post-BCG (p = 0.004); high SIRI predicted recurrence within 48 months (p = 0.05). Conclusions: High PLR and SIRI levels were associated with recurrence. Our findings support the emerging role of IFs in predicting BC outcomes and suggest their potential inclusion in future prognostic models. Full article

Background/Objectives: With evolving guidelines favoring de-escalation in the management of papillary thyroid microcarcinoma (PTMC), options such as active surveillance and minimally invasive procedures are now considered for patients with low-risk disease. However, a subset of PTMCs—particularly non-incidental cases—may exhibit aggressive behavior. This study compares disease characteristics and outcomes between incidental and non-incidental PTMCs over a 10-year period. Methods: This is a single-center retrospective comparative analysis utilizing a prospectively collected database of patients referred for thyroid surgery. Results: Papillary thyroid carcinoma accounted for 86.7% of thyroid malignancies, with PTMC comprising 36.2% (137 patients). Incidental PTMC represented 109 out of 1012 patients undergoing surgery for benign thyroid disease (10.8%). Non-incidental PTMC (NIPTMC), diagnosed preoperatively and presenting clinically without coexisting thyroid disease, was identified in 28 patients (20.4%). NIPTMCs were more frequently associated with high-risk features (75% vs. 10.1%, p = 0.004), including extrathyroidal extension (21.43% vs. 7.3% p = 0.0015), positive central lymph nodes (21.43% vs. 2.8%, p = 0.0291), positive lateral lymph nodes (28.6% vs. 0% p = 0.012), and lymphovascular invasion (3.6% vs. 0%). Multifocal PTMC was seen in 37 patients (27%), of which 27 had bilobar disease. Multifocal tumors had a higher likelihood of high-risk features (48.6% vs. 14%, p = 0.007). NIPTMC was a significant predictor of multifocality (p = 0.0098). All patients underwent surgery, none opted for active surveillance. Conclusions: NIPTMC is more often associated with high-risk features and multifocality, necessitating more extensive surgery. These findings emphasize the need for careful preoperative risk stratification to guide individualized management. Full article

Background/Objectives: Papillary thyroid carcinoma (PTC) accounts for the majority of thyroid cancers, with lymph node metastasis, including skip metastasis (SM), playing a crucial role in guiding prognosis and therapeutic planning. SM, characterized by lateral lymph node spread in the absence of central compartment involvement, has been observed in PTC with a wide range of reported frequencies. The identification of risk factors for SM is crucial for preoperative evaluation and surgical planning. This research aims to explore the clinicopathological features and potential risk factors linked to SM in patients with PTC, while also offering valuable insights for preoperative risk evaluation. Methods: A retrospective cohort study was conducted on 81 PTC patients who underwent central and lateral cervical lymph node dissection (LND) in our center. Clinical, demographic, and pathological data, including age, sex, tumor size, location, subtype, extrathyroidal extension, lymphovascular invasion, and the number of lymph node metastases were analyzed. Clinicopathological characteristics were analyzed between SM-positive and SM-negative patient groups using suitable statistical methods. Additionally, a regression analysis was performed to identify the risk factors for SM. Results: Of the 81 patients, 17.3% (n = 14) were diagnosed with skip metastasis (SM). The SM-positive group had a significantly higher age (p = 0.006), smaller tumor size (p < 0.001), and higher rates of extrathyroidal extension (p = 0.006). The proportion of female patients was elevated in the SM-positive group, but this observation did not achieve statistical significance (p = 0.128). Tumors located in the upper pole were more common in the SM-positive group (p = 0.016). Multivariate analysis revealed that female sex, older age, and tumor location in the upper pole were significant risk factors for SM (p = 0.031, p = 0.004, and p = 0.017, respectively), while a lower number of lateral lymph node metastases was significantly associated with SM (p = 0.010). Additionally, an age over 43.5 years predicted SM with a sensitivity of 78.6% and a specificity of 72.7%. Conclusions: Skip metastasis is not uncommon in PTC and may be associated with older age, female sex, upper pole tumor location, and fewer lateral lymph node metastases. Recognizing these factors during preoperative assessment may aid in anticipating atypical lymphatic spread patterns and optimizing surgical strategies. Full article

Background/Objectives: While sublobar resection (SLR) is accepted for selected small, early non-small-cell lung cancers (NSCLCs), its efficacy for tumors with visceral pleural invasion (VPI) remains debated. This study aimed to compare lung-cancer-specific survival (LCSS) between SLR and lobectomy in pT2a (tumor ≤ 3 cm with VPI) N0M0 NSCLCs from a nationwide population-based database. Methods: This retrospective study utilized Taiwan Cancer Registry data from 2011 to 2018, selecting patients with pT2a (tumor ≤ 3 cm with VPI) N0M0 NSCLC that underwent SLR or lobectomy, with specific exclusion criteria. Propensity score matching (1:1) was performed using a greedy algorithm with a 0.01 caliper width. LCSS was compared using Kaplan–Meier analysis with log-rank tests and Cox proportional hazards models before and after matching. Results: In the 2460-patient cohort (624 SLR, 1836 lobectomy) before matching, lobectomy was associated with significantly better overall (p = 0.01) and PL1 VPI subgroup (p = 0.009) LCSS. In the matched cohort (523 pairs), no significant difference in LCSS was observed between SLR and lobectomy, either overall (p = 0.21) or when stratified by PL1 (p = 0.11) or PL2 (p = 0.94) status. Multivariate Cox analysis in the matched cohort confirmed no significant association between surgery type and LCSS (adjusted HR 0.75, 95% CI 0.52–1.08, p = 0.124), but older age (>75 years), PL2 VPI, and lymphovascular invasion were independent predictors of worse LCSS (all p < 0.001). Conclusions: This large population-based study, after rigorous adjustment for confounders, found that SLR and lobectomy provided comparable LCSS. SLR may be an alternative for selected patients, but prospective validation is recommended. Full article

Background and Objectives: The therapeutic effect of para-aortic lymphadenectomy in patients with clinically para-aortic node-negative diseases remains controversial. In this study, we investigated whether combined pelvic and para-aortic lymphadenectomy has a survival benefit compared with pelvic lymphadenectomy alone in patients with clinically FIGO stage IIIC1 high-grade endometrial cancer. Materials and Methods: We retrospectively reviewed patients with clinically FIGO stage IIIC1 high-grade endometrial cancer in the period between January 2000 and December 2020 at two tertiary centers. The patients were stratified according to type of lymphadenectomy and subgroup analyses performed. Kaplan–Meier analysis and a Cox proportional-hazards model were used to evaluate survival outcomes. Results: A total of 56 patients were identified. Of these patients, 18 underwent pelvic lymphadenectomy alone and 38 underwent combined pelvic and para-aortic lymphadenectomy. After staging surgery, 34 (60.7%) patients had pathologically confirmed lymph node metastases. Within a median follow-up of 57.5 months, there were no significant differences in recurrence-free survival (RFS) and overall survival (OS) between the two groups. In subgroup analyses, the node- and lymphovascular space invasion (LVSI)-positive patients characterized by grade 3 endometrioid histologic type (p = 0.010) or negative peritoneal washing cytology (p = 0.035) had an RFS benefit from combined pelvic and para-aortic lymphadenectomy. Conclusions: The addition of para-aortic lymphadenectomy to pelvic lymphadenectomy did not improve survival in patients with clinically FIGO IIIC1 endometrial cancer. However, para-aortic lymphadenectomy may have RFS benefit for patients with grade 3 endometrioid histologic type and positive LVSI. Full article

Background: The risk of recurrence of early-stage cervical cancer (CC) is associated with prognostic factors such as tumor size, lymphovascular space invasion (LVSI), and deep stromal invasion (DSI). However, the adjuvant pelvic radiotherapy (RT) following surgery to reduce the risk of recurrence in “intermediate risk” remains controversial. This study aims to evaluate the role of adjuvant RT in the recurrence and identify prognostic factors. Methods: A systematic search of PubMed, Embase, and Cochrane databases was performed to identify studies comparing adjuvant RT versus no adjuvant treatment in early-stage CC patients with intermediate-risk factors defined by GOG-92 criteria. Outcomes were recurrence, local recurrence, death, 5-year overall survival (5y-OS), and 5-year disease-free survival (5y-DFS). Tumor size ≥ 4 cm, LVSI, and DSI were also evaluated as prognostic factors for recurrence. Statistical analysis was performed using Review Manager 7.2.0. Heterogeneity was assessed with I² statistics. Results: A total of 1504 patients from nine studies were included; only one study was a randomized controlled trial, while the others were retrospective cohorts. Adjuvant RT was used to treat 781 patients (52%). Median follow-up ranged from 48 to 120 months. Recurrence (OR 0.75; 95% CI 0.38–1.46; p = 0.39), local recurrence (OR 0.73; 95% CI 0.44–1.20; p = 0.22), death (OR 0.97; 95% CI 0.52–1.80; p = 0.91), 5y-OS (OR 1.22; 95% CI 0.36–4.18; p = 0.75), and 5y-DFS (OR 0.78; 95% CI 0.42–1.43 p = 0.42) revealed no statistically significant differences between adjuvant RT and observation groups. TS ≥ 4 cm was an independent prognostic risk factor for recurrence (HR 1.83; 95% CI 1.12–2.97; p = 0.02). Conclusions: Our findings suggest that adjuvant RT does not reduce recurrence risk in early-stage cervical cancer. Consider TS ≥ 4 cm as a significant prognostic factor for recurrence. Adjuvant RT in intermediate-risk patients should be considered with caution due the lack of significant improvement in recurrence until the CERVANTES and GOG-0263 trial results become available. Full article

Background/Objectives: To develop a nomogram for predicting tumor aggressiveness and the presence of lymphovascular space involvement (LVSI) in patients with endometrial cancer (EC) using preoperative MRI and pathology–laboratory data. Methods: This IRB-approved, retrospective, multicenter study included 245 patients with histologically confirmed EC who underwent preoperative MRI and surgery at participating institutions between January 2020 and December 2024. Tumor type and grade, both from preoperative biopsy and surgical specimens, as well as preoperative CA125 and HE4 levels, were retrieved from institutional databases. A preoperative MRI was used to assess tumor morphology (polypoid vs. infiltrative), maximum diameter, presence and depth (< or >50%) of myometrial invasion, cervical stromal invasion (yes/no), and minimal tumor-to-serosa distance. The EC-to-uterus volume ratio was also calculated. Results: Among the 245 patients, 27% demonstrated substantial LVSI, and 35% were classified as aggressive on final histopathology. Multivariate analysis identified independent MRI predictors of LVSI, including cervical stromal invasion (OR = 9.06; p = 0.0002), tumor infiltration depth (OR = 2.09; p = 0.0391), and minimal tumor-to-serosa distance (OR = 0.81; p = 0.0028). The LVSI prediction model yielded an AUC of 0.834, with an overall accuracy of 78.4%, specificity of 92.2%, and sensitivity of 43.1%. For tumor aggressiveness prediction, significant predictors included biopsy grade (OR = 8.92; p < 0.0001), histological subtype (OR = 12.02; p = 0.0021), and MRI-detected serosal involvement (OR = 14.39; p = 0.0268). This model achieved an AUC of 0.932, with an accuracy of 87.0%, sensitivity of 79.8%, and specificity of 91.2%. Both models showed excellent calibration (Hosmer–Lemeshow p > 0.86). Conclusions: The integration of MRI-derived morphological and quantitative features with clinical and histopathological data allows for effective preoperative risk stratification in endometrial cancer. The two nomograms developed for predicting LVSI and tumor aggressiveness demonstrated high diagnostic performance and may support individualized surgical planning and decision-making regarding adjuvant therapy. These models are practical, reproducible, and easily applicable in standard clinical settings without the need for radiomics software, representing a step toward more personalized gynecologic oncology. Full article

Introduction: Ampullary adenocarcinomas (AMPACs) represent rare malignant neoplasms arising in the Ampulla of Vater. Due to a lack of prospective studies and heterogeneous results from retrospective analyses, the outcomes of adjuvant chemotherapy (AC) in AMPAC are unclear. Methods: Pooled, pseudonymized data were retrieved from clinical cancer registries participating in the German Cancer Registry Group of the Association of German Tumor Centers (GCRG/ADT). Patients who underwent surgical resection of AMPACs (ICD-10: C24.1) with subsequent follow-up or AC were included. Patients with 90-day postoperative mortality were excluded. The epidemiologic and histopathologic features as well as the overall survival and recurrences were compared in both groups using R statistics. Results: In total, 830 patients with AMPACs were identified, of which 184 (22.2%) received AC. The surgery + AC patients showed more advanced tumor stages and more pronounced locoregional invasion as compared to the group undergoing surgery alone. AC was independently associated with an improved overall survival (OS) in a multivariable analysis (HR 0.57, p < 0.001), where pT3-4 status, lymph node metastases, vascular invasion, and advanced grading remained independent prognostic factors for OS. In the subgroup analyses, AC was associated with improved OS in the patients with pT3-4 tumors, lymph node metastases, lymphovascular invasion, and advanced grading, or UICC stage III, whereas no association with the OS was observed in the other subgroups. AC was also associated with superior disease-free survival (DFS) in a multivariable analysis. Conclusions: We provide a large-scale population-based analysis of AMPAC patients, showing an association of AC with improved OS in patients with advanced-staged disease or signs of locoregional invasion as compared to surgery alone. Full article

Background/Objectives: Endometrial cancer (EC) is the most common malignancy of the female genital tract. In 2013, The Cancer Genome Atlas analyzed the molecular profile of endometrial tumors identifying four risk classes (POLE ultramutated, mismatch repair-deficient, copy-number low-microsatellite stable, and copy-number high-serous-like. This classification is reshaping the current understanding of EC, enabling more refined risk stratification and uncovering potential therapeutic targets tailored to specific molecular subgroups. In the context of these four categories, it is possible to identify different molecular alterations that correlate with different prognoses. Methods and Results: We retrospectively analyzed tissue samples from eighty-five EC patients, performing multigene profiling using a 50-gene next-generation sequencing (NGS) panel to categorize them into distinct molecular subtypes; we observed the following distribution: 5.9% POLE, 25.8% mismatch repair-deficient/microsatellite instability (MMRd/MSI), 11.8% p53abn/TP53mut, and 56.5% NSMP. A favorable concordance (97.6%) was shown in MSI NGS-based analysis and MMR IHC results, and the agreement rate of p53 IHC and TP53 mutation was 92.3%. When we analyzed the correlation between molecular subtypes and clinicopathological features, we found that molecular subtypes significantly differentiated by grade, FIGO stage, and lymphovascular invasion (LVSI). These findings seem to support the effectiveness of our NGS-based classifier and its reliability in distinguishing both MSI and TP53 mutated cancers. This study also explored mutations in PIK3CA, PTEN, KRAS, ERBB2, and ESR1 genes, noting their potential as targets for treatments. PIK3CA mutations were linked to favorable features, such as early disease stage and absence of LVSI. Conclusions: Our study highlights the potential of a medium-complexity NGS panel for supporting the molecular classification of endometrial cancer, complementing the existing diagnostic algorithms. By identifying additional biomarkers, we provided valuable insights into the genomic landscape of EC. However, further exploration of the molecular profiles is needed to validate these findings and improve the identification of patients at a higher risk of unfavorable outcomes. Full article