Search Results (4,722)

Background/Objectives: Cribriform architecture is an adverse Gleason pattern 4 morphology associated with aggressive prostate cancer outcomes. Tertiary Gleason pattern 5, even as a minor component, may also identify tumors with higher-grade biology not fully captured by conventional Grade Group assignment. We examined whether cribriform architecture is associated with tertiary Gleason pattern 5 in patients undergoing radical prostatectomy. Methods: We performed a retrospective cross-sectional study of radical prostatectomy specimens from patients with prostate adenocarcinoma who underwent radical prostatectomy and had available clinicopathologic data. A centralized pathology review of digitized radical prostatectomy slides was used to assess cribriform architecture. Tertiary Gleason pattern 5 status was obtained from original pathology reports. Multivariable logistic regression was used to evaluate the association between cribriform architecture and tertiary Gleason pattern 5 after adjustment for age, preoperative prostate-specific antigen level, prostatectomy Gleason score, pathologic tumor stage, and margin status. Results: Among 303 patients, 47 (15.5%) had tertiary Gleason pattern 5. Cribriform architecture was more common in tumors with tertiary Gleason pattern 5 than in those without (70% vs. 21%; p < 0.001). On multivariable analysis, cribriform architecture remained independently associated with tertiary Gleason pattern 5 (adjusted odds ratio of 9.46; 95% confidence interval of 4.49–21.0; p < 0.001). The model demonstrated good discrimination, with an area under the receiver operating characteristic curve of 0.80. Conclusions: Cribriform architecture was strongly associated with tertiary Gleason pattern 5. These findings suggest that cribriform-positive tumors may be more likely to harbor minor high-grade pattern 5 components. Full article

Copper (Cu)–zinc (Zn) imbalance has been implicated in colorectal cancer (CRC). Exchangeable copper (exCu), the labile circulating Cu fraction, may better reflect functionally relevant metal dysregulation than total Cu. We investigated sex-specific associations between systemic Cu–Zn indices, tumor burden, and epithelial–mesenchymal transition (EMT)-related tissue remodeling in CRC. We studied 152 CRC patients and 140 healthy controls. Serum Cu, Zn, and exCu were measured using validated analytical methods; circulating gonadotropins, sex steroids, and carcinoembryonic antigen were also assessed. EMT-related proteins (E-cadherin, vimentin, fibronectin, vinculin, MEMO1) were quantified by Western blot in paired tumor and adjacent mucosa. Analyses were sex-stratified and age-adjusted. CRC patients exhibited higher serum Cu and exCu and lower Zn than controls, resulting in a marked increase in the exCu:Zn ratio in both sexes. In patients, exCu:Zn was associated with tumor burden and pathological stage, with stronger associations with tumor size and pT stage in women and with metastatic status in men. Serum exCu:Zn was associated with tumor − normal differences in EMT-related proteins, particularly ΔE-cadherin, in both sexes. Systemic Cu–Zn disequilibrium, summarized by the exCu:Zn ratio, was associated with tumor burden and epithelial remodeling in CRC in a sex-specific manner, suggesting its potential as a biologically informative biomarker warranting further validation. Full article

Background: Response to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) varies considerably, and oxidative stress may modulate radiosensitivity. This study evaluated ischemia-modified albumin (IMA) and thiol–disulfide homeostasis as potential biochemical predictors of pathological tumor regression. Methods: A prospective observational cohort study was conducted to assess pre- and post-treatment oxidative stress biomarkers in patients with LARC receiving capecitabine-based long-course CRT. Serum IMA, native thiol, total thiol, and disulfide levels were quantified spectrophotometrically. Pathologic regression was graded according to the Modified Ryan system as good (TRG 0–1) or poor (TRG 2–3). Receiver operating characteristic (ROC) analyses, Firth-penalized logistic regression, and internal validation using cross-validation, calibration, and decision-curve analyses were performed. Results: Of 38 screened patients, 31 met eligibility criteria and completed CRT, alongside 31 matched healthy controls. Compared with controls, patients had higher baseline disulfide (15.7 ± 5.2 vs. 11.9 ± 3.1 µmol/L; p = 0.012) and IMA levels (0.886 ± 0.062 vs. 0.798 ± 0.048 ABSU; p = 0.006). Poor responders exhibited higher pre-treatment IMA (0.927 ± 0.045 vs. 0.842 ± 0.050 ABSU; p = 0.020) and disulfide levels (18.4 ± 5.2 vs. 13.0 ± 3.8 µmol/L; p = 0.012). Pre-treatment IMA demonstrated the highest predictive accuracy for poor tumor regression (AUC = 0.872; 95% CI 0.751–0.993). In multivariable Firth-penalized logistic regression, elevated baseline IMA was independently associated with poor pathological response (OR = 3.63; 95% CI 1.22–16.20; p = 0.043), whereas negative circumferential resection margin (CRM) status was independently associated with favorable regression (OR = 0.21; 95% CI 0.02–0.71; p = 0.003). The internally validated model demonstrated excellent discrimination (AUC = 0.948; 95% CI 0.866–0.966) and good calibration. Conclusions: Baseline IMA and CRM status were independently associated with pathological response after CRT in LARC. These findings suggest that oxidative-stress biomarkers may have potential value for response stratification; however, the results should be considered exploratory and require external validation in larger independent cohorts before clinical application. Full article

Hashimoto thyroiditis (HT) coexists with differentiated thyroid carcinoma (DTC), particularly papillary thyroid carcinoma, in approximately 25% of cases. However, the impact of this association on DTC outcomes remains controversial. The aim of this study was to analyze the influence of Hashimoto thyroiditis on disease-specific survival (DSS) and recurrence-free survival (RFS) in DTC patients. Methods: A retrospective study conducted at our institution between 2007 and 2020 analyzed 707 DTC patients treated with surgery and/or I-131 therapy. Cox proportional hazards regression was used to identify independent predictors, including sex, age, tumor histology, HT status, and initial TNM stage. Results: Among 707 DTC patients, 628 (88.8%) had papillary cancer, 582 (82.3%) were female, 395 (55.9%) were <55 years old; HT coexisted in 137 (19.4%) patients. During follow-up, 23 (3.25%) developed recurrent disease; at last follow-up, 638 (90.2%) were alive. Initial distant metastases (p < 0.001) and higher T stage (p = 0.002) independently predicted worse DSS. For RFS, male sex (p = 0.015), higher T stage (p = 0.018), and lymph node involvement (p = 0.023) independently predicted an increased risk of recurrence. HT was not an independent predictor of DSS (HR 0.97, 95% CI 0.21–4.52; p = 0.964) or recurrence (HR 0.36, 95% CI 0.05–2.73; p = 0.322). Conclusions: Although Hashimoto thyroiditis was associated with favorable clinicopathological features, it was not independently associated with disease-specific or recurrence-free survival. Conventional staging parameters, particularly tumor stage, remain the principal determinants of prognosis in differentiated thyroid cancer. Full article

Background and Objectives: Evidence linking sarcopenia and myosteatosis to oncological outcomes in renal cell carcinoma (RCC) remains inconsistent. We aimed to evaluate whether preoperative psoas muscle measurements are associated with tumor stage, recurrence, and survival in RCC patients undergoing nephrectomy. Materials and Methods: A total of 199 patients who underwent nephrectomy with a diagnosis of RCC between 2018 and 2024 were retrospectively evaluated. Preoperative computed tomography images were used to measure the bilateral psoas muscle area at the L3 vertebral level and Hounsfield unit (HU) values. The psoas muscle index (PMI) was calculated. PMI and psoas HU values were analyzed as continuous variables, as this approach preserves statistical information and avoids misclassification bias inherent to arbitrary dichotomization, particularly given the absence of population-specific validated thresholds for Turkish RCC patients. Tumor stage, metastasis, recurrence, and survival data were analyzed. Results: The mean age of the patients was 60.29 ± 11.62 years, and 67.84% were male. The mean PMI was 5.11 ± 1.54 cm²/m² while the mean psoas HU value was 38.63 ± 8.95 HU. PMI was significantly higher in patients with advanced-stage (T3 and T4) disease than in those with early-stage (T1 and T2) disease (5.57 ± 1.49 vs. 4.30 ± 1.28, p < 0.001). A positive correlation was found between T stage and PMI (r = 0.396, p < 0.001) and between tumor size and PMI (r = 0.215, p = 0.002). Modest but significant correlations were found between age and both PMI (r = −0.274, p < 0.001) and psoas HU values (r = −0.347, p < 0.001). Conclusions: In this retrospective nephrectomy series, conducted in a cohort inherently enriched for adequate performance status and surgical fitness, PMI showed a positive correlation with pathological T stage and tumor size, intriguingly higher PMI values were observed in patients with advanced T stages. These findings suggest that the role of psoas-based muscle measurements in the prognostication of this subset of RCC patients (advanced disease but candidates for surgical treatment) may be limited. Full article

Background: Biliary drainage is a key component of palliative management in patients with malignant biliary obstruction. In cases where endoscopic approaches are unsuccessful or cannot be performed, percutaneous transhepatic biliary drainage (PTBD) represents an established alternative for achieving biliary decompression. The C-reactive protein–albumin–lymphocyte (CALLY) index combines inflammatory, nutritional, and immune-related parameters into a single marker, while the modified Glasgow Prognostic Score (mGPS), based on C-reactive protein and albumin concentrations, reflects the systemic inflammatory status of the patient. This study aimed to evaluate the prognostic value of the preprocedural CALLY index and mGPS in predicting 30-day mortality among patients with advanced malignant biliary obstruction undergoing palliative PTBD. Methods: This single-center retrospective study was conducted in a total of 179 patients who underwent palliative PTBD for malignant biliary obstruction at Ankara Etlik City Hospital between December 2022 and June 2025. Results: The 30-day mortality rate was 25.1%. The cut-off value for CALLY was determined as 67 based on receiver operating characteristic (ROC) curve analysis, and mGPS was categorized as 0–1 versus 2. In univariable Cox regression analyses, pancreaticobiliary tumor type, mGPS = 2, and CALLY < 67 were associated with early mortality. In multivariable Cox analysis, CALLY ≥ 67 was independently associated with a reduced risk of 30-day mortality, whereas pancreaticobiliary tumor type was independently associated with an increased risk. In the CALLY–mGPS risk stratification, 30-day mortality rates were 8.0%, 13.5%, and 44.1% in the low-, intermediate-, and high-risk groups, respectively. Conclusions: In this retrospective cohort, preprocedural inflammation- and nutrition-based markers were found to be associated with early mortality in patients with malignant biliary obstruction undergoing PTBD. Accordingly, risk stratification using readily available parameters such as CALLY and mGPS appears feasible in the preprocedural setting. The CALLY–mGPS-based approach may provide a practical framework for clinical risk assessment; however, prospective multicenter validation, including tumor-specific subgroup analyses, is warranted. Full article

Background: Age at diagnosis and histologic differentiation are clinically relevant in early gastric cancer (GC), as poorly differentiated tumors and those diagnosed in younger patients often demonstrate more aggressive characteristics. Serum microRNAs (miRNAs) may provide insights into the molecular basis of these features. Methods: We compared expression profiles between undifferentiated and differentiated early GC cases to identify differentially expressed miRNAs (DEmiRNAs) and associated enriched pathways. Using Lasso regression, we developed and cross-validated a histologic differentiation classifier based on miRNA profiles from 1399 early GC serum samples. Finally, cancer-specific miRNA differences between adolescent and young adult (AYA) and non-AYA patients were evaluated using samples from cancer cases and normal controls. Results: We identified 75 differentiation-associated DEmiRNAs targeting genes enriched in cancer hallmark pathways such as TP53 and PI3K/AKT/mTOR signaling. In the validation set, the combined Lasso model predicted differentiation status with a sensitivity of 69.2%, specificity of 75.3%, positive predictive value (PPV) of 66.9%, negative predictive value (NPV) of 77.2%, an overall accuracy of 73.1%, and an area under the curve (AUC) of 79.7%. Comparison of AYA and non-AYA groups identified 52 cancer-specific and age-related miRNAs. Notably, three components of a previously reported four-miRNA GC diagnostic signature were significantly associated with age. Conclusions: Age-related variation in miRNA expression suggests that patient age may influence the performance of the existing four-miRNA diagnostic signature in early GC. Overall, our findings demonstrate the utility of miRNA profiling for predicting differentiation status in early GC and reveal age-associated variation in cancer-specific miRNAs. Full article

Background/Objectives: Spinal ependymoma is the most common intramedullary spinal cord tumor in adults, and maximal safe resection is the cornerstone of treatment. Patients aged 75 years and older are underrepresented in surgical neuro-oncology cohorts. We sought to characterize treatment patterns and identify predictors of overall survival in very elderly patients with spinal ependymoma. Methods: We performed a retrospective cohort study of patients aged 65 years or older with spinal ependymoma using the National Cancer Database. The primary cohort was patients aged 75 years or older (very elderly); patients aged 65–74 years served as a comparison cohort. Multivariable Cox proportional-hazards models were fit within each cohort, and a surgery-by-age-cohort interaction was tested. Results: Of 1497 eligible patients aged 65 years or older with spinal ependymoma, 422 patients (28.2%) met criteria for the final analytic cohort. Intramedullary versus extramedullary tumor status was not available in the NCDB PUF and therefore could not be characterized. Very elderly patients were less likely to undergo surgery than the comparison cohort (70% vs. 85%; p < 0.001) despite similar tumor characteristics. Among very elderly patients, median overall survival was 59.7 months without surgery and 106.0 months with surgery, an approximately 46-month difference favoring surgery. Surgery was independently associated with lower mortality (HR 0.46; 95% CI, 0.24–0.89; p = 0.021). Increasing age (HR 1.15 per year; 95% CI, 1.07–1.22; p < 0.001), Charlson–Deyo score ≥ 2 (HR 4.41; 95% CI, 1.65–11.79; p = 0.003), and increasing tumor size (HR 1.02 per mm; 95% CI, 1.01–1.04; p < 0.001) were also independently associated with worse survival. In the 65–74 cohort, no significant association between surgery and overall survival was detected (HR 1.23; 95% CI, 0.54–2.81; p = 0.623), though statistical power was limited by only 7 deaths in the no-surgery arm. The surgery-by-age-cohort interaction was significant (HR 0.37; p = 0.043). Conclusions: Surgical resection was independently associated with improved overall survival in very elderly patients with spinal ependymoma despite lower utilization. Chronological age alone may be an imperfect basis for excluding older adults from surgical consideration. Full article

Background: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine malignancy with a high risk of recurrence. While adjuvant radiotherapy is standard following surgical resection in high-risk disease, the additional benefit of platinum–etoposide chemotherapy and the prognostic role of tumor anatomical location remain uncertain. Methods: We conducted a multicenter retrospective cohort study including patients with high-risk MCC (stage IIB–III) treated with surgery followed by adjuvant radiotherapy with or without platinum–etoposide chemotherapy. Tumor sites were classified according to sun-exposure status. Disease-free survival (DFS) and overall survival (OS) were estimated using Kaplan–Meier methods and compared using the log-rank test, with subgroup analyses by anatomical region and stage. Results: A total of 103 patients were included, of whom 77 (74.8%) received adjuvant chemoradiotherapy and 26 (25.2%) received radiotherapy alone. Patients with non-sun-exposed tumors demonstrated longer survival outcomes than those with sun-exposed tumors, with a median DFS of 57 months versus 42 months (p = 0.15), and a median OS of 179 months versus 109 months (p = 0.054), respectively. Among patients with sun-exposed tumors, chemoradiotherapy was associated with numerically improved DFS (42 vs. 34 months; p = 0.051) and OS (128 vs. 98 months; p = 0.08) compared with radiotherapy alone. In patients with non-sun-exposed tumors, chemoradiotherapy demonstrated a more pronounced improvement in OS (178 vs. 56 months; p = 0.054), while DFS also favored combined treatment (49 vs. 78 months; p = 0.078). Conclusions: In this multicenter cohort, adjuvant chemotherapy did not demonstrate a uniform survival benefit overall but was associated with improved outcomes in head and neck MCC, suggesting a potential site-specific effect. Similar outcomes across stage III subgroups suggest that chemotherapy may mitigate stage-related prognostic differences. These findings support a selective approach to adjuvant chemotherapy and highlight the need for prospective studies incorporating modern immunotherapy strategies. Full article

Major depressive disorder (MDD) is a complex and heterogeneous psychiatric disorder with a high prevalence. Neuroinflammation may define biologically distinct patient subgroups with different mechanisms, clinical phenotypes, and treatment responses. This narrative review integrates current evidence around three linked questions: how neuroinflammatory processes contribute to depression, how biomarkers can identify clinically relevant inflammatory phenotypes, and how these findings can inform anti-inflammatory treatment strategies. The major mechanisms discussed include microglial activation and neuroimmune signaling, hypothalamic–pituitary–adrenal axis dysregulation and glucocorticoid receptor resistance, kynurenine pathway alterations, and cytokine-driven impairment of neurogenesis and synaptic plasticity. These pathways interact with stress responses, neurotransmitter systems, and neuronal function, while their expression may vary according to sex, age, hormonal status, disease stage, and treatment exposure. These interconnected pathways may contribute to depressive symptoms by disrupting neurotransmitter systems and impairing neural plasticity. In addition, this review discusses several candidate biomarkers, including C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF) and transforming growth factor-β1 (TGF-β), which may support patient stratification, treatment prediction, and assessment of target engagement. Clinical trials of anti-inflammatory agents have shown inconsistent and generally modest effects in unselected MDD populations. By integrating mechanistic evidence with biomarker-guided therapeutic implications, this review aims to clarify how neuroinflammatory research may inform more precise and individualized treatment strategies for depression. Full article

Background: Triple-negative breast cancer (TNBC) is a biologically heterogeneous disease. Clinically accessible biomarkers remain limited. Objective: To evaluate androgen receptor (AR) expression and immune response—stromal tumor-infiltrating lymphocytes (sTILs), CD4⁺, CD8⁺, CD4/CD8 ratio—to explore their clinicopathological associations and relationships with 3-year overall survival (OS) in TNBC. Methods: We retrospectively analyzed data from 86 treatment-naïve women with TNBC who were treated between 2012 and 2019 at a single academic center. AR and CD4/CD8 were assessed immunohistochemically; sTILs were scored on H&E following The International TIL Working Group recommendations. Survival analyses focused on 3-year OS, with follow-up truncated at 36 months and multivariable Cox regression restricted to non-metastatic disease (stage I–III). Results: High AR expression (≥10%) occurred in 23% of tumors and was associated with lower CD8⁺ infiltration and lower tumor grade. Across adjusted models, we did not demonstrate statistically significant and independent associations between AR or immune markers and 3-year OS; however, inference is limited by the low number of events (10 deaths). Conclusions: AR status was associated with the immune response, particularly with reduced CD8⁺ infiltration in AR-high tumors, supporting the concept of biologically distinct AR–immune phenotypes. The absence of statistically significant survival associations in adjusted analyses should be interpreted cautiously given the limited event counts, and larger prospective cohorts are needed to validate prognostic and potential therapeutic implications. Full article

Background: Homologous recombination deficiency (HRD) is emerging as a clinically relevant biomarker across diverse tumor types, in addition to ovarian cancer. In this study, we evaluated the genomic instability score (GIS) across multiple tumor types using the TruSight Oncology 500 HRD assay, which incorporates the Myriad Genetics GIS algorithm, a widely used reference standard for HRD assessment. Methods: A total of 162 tumor samples (17 ovarian cancers and 145 non-ovarian tumors) underwent next-generation sequencing using the TruSight Oncology 500 HRD assay. Results: A total of 14 tumors were classified as GIS-High, defined as a GIS score ≥42, representing 8.6% of all cases. Among ovarian cancers, 7 out of 17 cases (41.2%) met the GIS-High threshold. Among non-ovarian tumors, seven GIS-High tumors were identified, accounting for 4.8% of cases (7/145). GIS-High cases occurred in breast (n = 4), lung (n = 2), and hepatobiliary tract (n = 1) cancers. GIS scores showed significant associations with BRCA1/2 and TP53 mutational status. In contrast, alterations in HRD-related genes other than BRCA1/2 did not show significant associations with GIS score. Conclusions: GIS-High tumors were identified in a small subset of non-ovarian cancers. These findings support further investigation of GIS as an exploratory biomarker of HRD-like genomic scarring beyond ovarian cancer, but its predictive and therapeutic relevance in non-ovarian tumors requires additional validation. Full article

Background: Accurate prognostication in terminal cancer patients receiving best supportive care (BSC) is essential for guiding end-of-life decision-making and avoiding non-beneficial interventions. Several prognostic models have been developed for advanced cancer, including the Palliative Prognostic Index (PPI) and the Objective Prognostic Score (OPS). However, prospective data evaluating their performance specifically in patients managed with BSC are limited. This study evaluated the prognostic performance of PPI and OPS in terminal cancer patients receiving BSC. It also examined whether their combined use provides additional value for short-term mortality risk stratification. Methods: This prospective observational cohort study included hospitalized adult patients with terminal-stage cancer and a documented BSC decision. Terminal-stage cancer was operationally defined as stage IV malignancy with poor performance status and no remaining feasible disease-directed oncological treatment option due to severe clinical deterioration and/or major organ dysfunction. Patients were prospectively enrolled from 12 April 2024 to 13 December 2024 and followed until death. Eligible patients had poor Eastern Cooperative Oncology Group performance status (ECOG 3–4) and had not received oncologic treatment within the preceding month. PPI and OPS were calculated at baseline using predefined criteria. Survival time was defined as the interval between baseline assessment and death. The prognostic performance of the scores for 3-, 4-, and 6-week mortality was evaluated, and survival outcomes were analyzed using standard survival analysis methods. Results: A total of 112 patients were included in the final analysis. The mean age was 62.3 ± 12.3 years; 66 patients (58.9%) were male and 46 (41.1%) were female. The most common primary tumor sites were colon cancer (20.5%), non-small cell lung cancer (17.0%), and gastric cancer (15.2%). Both PPI > 6 and OPS ≥ 3 were associated with higher short-term mortality, although their individual discriminatory performance was modest. The combined OPS–PPI approach showed statistically significant but still modest discrimination at all time points. Although this difference was limited, the combined approach supported the stratification of a clinically relevant subgroup at particularly high risk of imminent death. Patients with both OPS ≥ 3 and PPI > 6 had the poorest survival, with a median overall survival (OS) of 11 days. In multivariable Cox regression analysis, the combined high-risk group remained independently associated with poorer OS (HR 1.53, 95% CI 1.01–2.31; p = 0.046). Conclusions: Although the individual discriminatory performance of PPI and OPS was modest, their combined use may provide additional risk stratification value and may help identify patients at particularly high risk of short-term mortality among terminal cancer patients receiving BSC. These findings should be interpreted as supporting bedside risk stratification rather than indicating a definitive individual-level prediction model. Full article

Background and Objectives: Magnetic resonance imaging (MRI) is essential for monitoring patients with diffuse gliomas after surgery and adjuvant therapy. However, the prognostic significance of imaging findings observed on the first post-treatment MRI remains incompletely defined in routine clinical practice. This study aimed to evaluate whether MRI features identified on the first post-treatment examination are associated with recurrence-free survival after near-total resection (NTR), defined for this real-world cohort as ≥80% volumetric tumor removal (which differs from the RANO Resect Group definition of GTR). Materials and Methods: Consecutive adult patients with histologically confirmed diffuse gliomas diagnosed between 2021 and 2024 were screened for eligibility (n = 283) and classified according to the 2021 WHO Classification of Tumors of the Central Nervous System. The first post-treatment MRI was defined as the earliest follow-up examination performed after completion of all initially planned therapy (surgery alone in patients without indication for adjuvant therapy; post-radiotherapy ± chemotherapy in the remaining patients), and not the immediate postoperative scan. Patients with available first post-treatment MRI were included (n = 149), resulting in a final cohort of 139 cases after exclusion of outliers. The evaluated MRI corresponded to the first follow-up examination after treatment (mean interval ~120 days after surgery). Logistic regression models were used to assess associations between post-treatment MRI features and recurrence-free survival at one and two years after NTR, with exploratory analyses for reoperation and reirradiation. Results: Residual tumor identified on the first post-treatment MRI was associated with lower odds of recurrence-free survival (RFS) at one and two years after NTR. Postoperative functional status also demonstrated an independent association with tumor control. Other imaging variables showed associations in univariable analyses but did not remain independent predictors after adjustment. Exploratory analyses of reoperation and reirradiation suggested additional clinical influences, including patient age. Conclusions: In this real-world cohort with heterogeneous tumor subtypes and treatment regimens, residual tumor on first follow-up MRI was the most consistent imaging correlate of reduced RFS, alongside postoperative functional status. These hypothesis-generating findings should be validated in stratified, prospective cohorts. Full article

Background and Objectives: Uterine carcinosarcoma (UCS) is a rare and highly aggressive gynecologic malignancy with poor clinical outcomes and limited therapeutic options. This study investigated the prognostic significance of molecular subgroups defined by p53 expression and mismatch repair (MMR) status in UCS. Materials and Methods: This retrospective study included 51 patients with uterine carcinosarcoma who underwent surgical treatment between 2010 and 2023. Immunohistochemical analyses were performed to evaluate p53 expression (wild-type vs. aberrant) and MMR status (intact vs. deficient). Patients were classified into four molecular subgroups: p53wt/MMR-intact (n = 15), p53abn/MMR-intact (n = 24), p53wt/MMR-deficient (n = 9), and p53abn/MMR-deficient (n = 3). Clinicopathological characteristics, overall survival (OS), and disease-free survival (DFS) were analyzed. Additional component-specific analyses were performed for carcinomatous and sarcomatous tumor elements. Results: The median follow-up period was 34 months, and the overall mortality rate was 51.0%. Patients with p53wt/MMR-deficient tumors demonstrated the most favorable outcomes, with a mean OS of 92.9 ± 22.1 months and a mortality rate of 33.3%. In contrast, the p53abn/MMR-intact subgroup showed the poorest survival outcomes (mean OS: 54.4 ± 11.6 months; mortality rate: 62.5%). Although Kaplan–Meier survival analysis did not demonstrate statistically significant differences between molecular subgroups (p = 0.783), distinct prognostic trends were observed. Multivariate Cox regression analysis identified age and lymph node involvement as independent predictors of both OS and DFS. Component-specific analyses demonstrated significant associations between aberrant p53 expression in the carcinomatous component and epithelial subtype distribution (p = 0.025) as well as myometrial invasion patterns (p = 0.040). Conclusions: Combined p53/MMR-based immunohistochemical classification demonstrated distinct prognostic trends in uterine carcinosarcoma. These findings suggest that molecular stratification could support risk assessment and therapeutic decision-making in UCS. Larger prospective multicenter studies are warranted to validate these findings and clarify their potential clinical implications. Full article