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Keywords = clinicopathological studies

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18 pages, 4365 KB  
Article
Stage-Specific miRNA Profiling Reveals Key Regulators of EMT and EGFR-TKI Resistance in Gallbladder Cancer
by Neeraj Saklani, Puja Sakhuja, Surbhi Goyal, Anil Kumar Agarwal, Sarangadhara Appala Raju Bagadi and Poonam Gautam
Cancers 2026, 18(3), 502; https://doi.org/10.3390/cancers18030502 - 3 Feb 2026
Abstract
Background: Gallbladder cancer (GBC) is a highly aggressive malignancy characterized by a poor prognosis, particularly in its advanced stages. While microRNAs (miRNAs) regulate cancer progression, their specific role in the transition from early to advanced GBC is poorly understood. Methods: We performed miRNA [...] Read more.
Background: Gallbladder cancer (GBC) is a highly aggressive malignancy characterized by a poor prognosis, particularly in its advanced stages. While microRNAs (miRNAs) regulate cancer progression, their specific role in the transition from early to advanced GBC is poorly understood. Methods: We performed miRNA expression profiling on 41 formalin-fixed paraffin-embedded (FFPE) tissues, including 10 gallstone disease (GSD) controls, 14 early-stage GBC (stage I and II), and 17 advanced-stage GBC cases (stage III and IV), using the NanoString nCounter platform. Differentially expressed miRNAs (DEMs) were identified followed by miRNA target identification using miRTarBase. Results: We identified 43 significantly dysregulated miRNAs in early-stage and 46 in advanced-stage GBC compared to controls. Based on the literature search, we found EMT-inhibiting miRNAs (miR-200 family) to be overexpressed in early stage and downregulated in advanced stages (miR-574-3p, miR-195-5p) in our study. Pathway analysis revealed significant enrichment of the ‘EGFR tyrosine kinase inhibitor resistance’ pathway in both the stages. The correlation of DEMs with clinicopathological features revealed that the expression of miR-361-3p and miR-423-5p was significantly associated with tumor grade (r = −0.605, p = 0.0003) and lymph node status (r = −0.621, p = 0.0001), respectively. Conclusions: This study identifies distinct miRNA signatures associated with GBC initiation and progression, offering insights into the molecular pathogenesis of the disease. Furthermore, functional studies of the miRNAs implicated in EMT and EGFR-TKI resistance may be conducted using GBC cell lines to dissect the precise roles of key miRNAs and explore their potential as novel therapeutic targets in GBC. Full article
(This article belongs to the Special Issue MicroRNA (miRNA) in Cancers)
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12 pages, 359 KB  
Article
Detection of TERT Promoter Mutations in Papillary Thyroid Carcinoma Using Droplet Digital PCR and Their Association with Aggressive Tumor Features
by Jeongmin Lee, Chaiho Jeong, Jeonghoon Ha, Dong-Jun Lim, Tae-Jung Kim and Ki-Hyun Baek
Int. J. Mol. Sci. 2026, 27(3), 1497; https://doi.org/10.3390/ijms27031497 - 3 Feb 2026
Abstract
This study evaluated the reliability of droplet digital polymerase chain reaction (ddPCR) for detecting TERT promoter (pTERT) mutations in formalin-fixed, paraffin-embedded (FFPE) thyroid cancer samples and examined their association with clinicopathological features. A retrospective cohort of 296 postoperative patients with papillary thyroid carcinoma [...] Read more.
This study evaluated the reliability of droplet digital polymerase chain reaction (ddPCR) for detecting TERT promoter (pTERT) mutations in formalin-fixed, paraffin-embedded (FFPE) thyroid cancer samples and examined their association with clinicopathological features. A retrospective cohort of 296 postoperative patients with papillary thyroid carcinoma (PTC) was analyzed. DNA extracted from archived FFPE thyroidectomy specimens was examined for TERT promoter mutations using ddPCR. pTERT mutations were detected in 14 cases (4.7%). Tumors harboring pTERT mutations were significantly larger than wild-type tumors (1.5 ± 1.3 cm vs. 1.0 ± 0.7 cm, p = 0.012) and showed higher frequencies of extrathyroidal extension (78.6% vs. 55.0%, p = 0.028), capsular invasion (85.7% vs. 63.1%, p = 0.036), and lymph node metastasis (64.3% vs. 44.0%, p = 0.012). Multivariate analysis demonstrated that increasing age (odds ratio (OR), 1.07; 95% confidence interval (CI), 1.01–1.13; p = 0.015), tumor size (OR, 1.86; 95% CI, 1.12–3.08; p = 0.016), and lymph node metastasis (OR, 3.50; 95% CI, 1.09–6.53; p = 0.026) were independently associated with pTERT mutations. ddPCR enables sensitive detection of pTERT mutations in archived FFPE thyroid cancer specimens and identifies tumors with aggressive clinicopathological features, supporting its utility for postoperative risk stratification in clinical practice. Full article
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21 pages, 3314 KB  
Article
MMHC-OCPR: Prediction of Platinum Response and Recurrence Risk in Ovarian Cancer with Multimodal Deep Learning
by Enyu Tang, Haoming Xia, Zhenlong Yuan, Yuting Zhao, Shengnan Wang, Zhenbang Ye, Shangshu Gao, Ziqi Zhou, Yuxi Zhao, Jia Zeng, Nenan Lyu, Jing Zuo, Ning Li, Jianming Ying and Lingying Wu
Biomedicines 2026, 14(2), 348; https://doi.org/10.3390/biomedicines14020348 - 2 Feb 2026
Viewed by 24
Abstract
Background/Objectives: Ovarian cancer has the highest mortality among gynecological malignancies, with platinum resistance significantly contributing to poor prognosis. We aimed to develop a multimodal model (MMHC-OCPR) to predict platinum response and recurrence risk, enabling earlier personalized treatment and improved outcomes. Methods: [...] Read more.
Background/Objectives: Ovarian cancer has the highest mortality among gynecological malignancies, with platinum resistance significantly contributing to poor prognosis. We aimed to develop a multimodal model (MMHC-OCPR) to predict platinum response and recurrence risk, enabling earlier personalized treatment and improved outcomes. Methods: This multicenter retrospective study included a combined cohort of 431 patients, comprising 1182 whole slide images (WSIs) curated from two independent datasets. The primary cohort consisted of 376 patients from the National Cancer Center (China), which was further partitioned into training, validation and internal test sets to ensure model development and evaluation. An additional external test cohort was incorporated using publicly available data from TCGA, enhancing the generalizability of our findings. We implemented a weakly supervised multiple instance learning framework to integrate histopathological imaging with clinicopathological variables, further strengthened by the incorporation of the transformer-based pretrained encoder UNI2-h, which enhanced the model’s predictive performance. Results: All patients in the primary cohort had pathology slides collected from primary ovarian tumors and metastatic tumor, along with clinical factors related to prognosis and treatment response. The baseline platinum response classifier using primary WSIs achieved an AUC of 0.896 in the internal test group and 0.876 in the external test group. Integration of metastatic WSIs and clinical data inputs yielded a superior AUC of 0.914 in the internal test set. The recurrence risk model demonstrated a C-index of 0.801, rising to 0.838 after multimodal enhancement. The model stratified patients into low-, intermediate- and high-risk groups with 2-year progression-free survival rates of 77.3%, 48.0% and 2.0%, respectively. Conclusions: Our model enables the early detection of platinum resistance, guiding timely treatment intensification. The recurrence risk stratification supports personalized management by identifying patients with favorable outcomes following surgery and chemotherapy, potentially sparing them from maintenance therapy to reduce associated toxicity, cost, and enhance quality of life. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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16 pages, 685 KB  
Article
Clinicopathological Features of Right vs. Left Colorectal Carcinomas: Do the Differences Really Matter?
by Aura Jurescu, Alis Dema, Sorina Tăban, Robert Barna, Adrian Ovidiu Văduva, Octavia Vița, Remus Cornea, Dorela-Codruța Lăzureanu, Anca Mureșan, Mărioara Cornianu, Bianca Natarâș, Ioana Hurmuz, Adelina Vidac and Sorin Dema
Life 2026, 16(2), 242; https://doi.org/10.3390/life16020242 - 2 Feb 2026
Viewed by 53
Abstract
Background and objectives: Colorectal cancer (CRC) presents a variety of molecular and pathological characteristics due to its location in the large intestine, which influences its management and prognosis. We aimed to evaluate the clinicopathological disparities between right colon (RCC), left colon (LCC), and [...] Read more.
Background and objectives: Colorectal cancer (CRC) presents a variety of molecular and pathological characteristics due to its location in the large intestine, which influences its management and prognosis. We aimed to evaluate the clinicopathological disparities between right colon (RCC), left colon (LCC), and rectal carcinomas. Materials and methods: A retrospective observational study was conducted to examine consecutive cases of colorectal carcinomas diagnosed at the “Pius Brinzeu” County Emergency Clinical Hospital (PBCECEHT), Romania. The clinicopathological characteristics and metastatic spread were analyzed by the site of the malignant tumor (right colon, left colon, or rectum). Results: A total of 1812 patients met the inclusion criteria, predominantly males (57.95%). Patients with RCC had an almost equal distribution between sexes, while patients with LCC and rectal carcinomas were more frequently males (p < 0.0001). RCC tumors were mostly high-grade (p < 0.0001), deeply invasive (p < 0.0001), and mucinous (p = 0.0109), with lymphovascular invasion and distant metastases. Conclusions: We observed different clinicopathological characteristics of CRC depending on the site of origin. We emphasize that tumor location is a parameter worth considering in CRC patients, both in therapeutic management and in future clinical trials. Full article
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15 pages, 4000 KB  
Article
Non-Surgical Causes of Death in the Emergency Department: A Five-Year Monocentric Clinicopathological Study
by Adrian-Iosif Moldoveanu, Diana Maria Orzata, Gabriel Veniamin Cozma, Radu Gheorghe Dan, Ovidiu Alexandru Mederle and Flavia Zara
Medicina 2026, 62(2), 293; https://doi.org/10.3390/medicina62020293 - 2 Feb 2026
Viewed by 59
Abstract
Background and objectives: Non-surgical deaths in the Emergency Department (ED) occur in the context of severe acute pathology and frequently under conditions of limited diagnostic time and incomplete clinical information. Data integrating ante-mortem clinical assessment with medico-legal autopsy results remain scarce, particularly [...] Read more.
Background and objectives: Non-surgical deaths in the Emergency Department (ED) occur in the context of severe acute pathology and frequently under conditions of limited diagnostic time and incomplete clinical information. Data integrating ante-mortem clinical assessment with medico-legal autopsy results remain scarce, particularly in Central and Eastern Europe. Materials and Methods: We conducted a retrospective, monocentric descriptive clinicopathological study including 45 consecutive non-surgical deaths occurring in the Emergency Department of a tertiary care hospital between January 2019 and December 2023. Clinical, biological, and temporal data were retrospectively analyzed and correlated with complete medico-legal autopsy findings in order to establish the cause of death and to assess clinicopathological concordance. Results: The mean patient age was 74.3 years, and the median time from ED admission to death was 142 min. Cardiovascular disease was the most frequent cause of death in this cohort (35.6%), followed by sepsis (22.2%), non-COVID respiratory causes (15.6%), and SARS-CoV-2 infection (17.8%). Complete clinicopathological concordance was observed in 37.8% of cases, while partial concordance predominated (57.8%). Total discordance was rare (4.4%). Autopsy findings frequently demonstrated multisystem involvement, particularly in deaths attributed to sepsis and COVID-19. Conclusions: In this descriptive, autopsy-based cohort, non-surgical deaths in the Emergency Department were associated with advanced disease severity and rapid clinical deterioration, limiting complete etiological clarification prior to death. The high rate of partial clinicopathological concordance may reflect the complexity of terminal pathophysiological mechanisms encountered in emergency settings. Systematic clinicopathological correlation through autopsy remains essential for understanding selected cases of acute non-surgical mortality in selected, rapidly fatal ED cases. Full article
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13 pages, 1411 KB  
Article
Renal Shear Wave Elastography for Differentiating Vasculitic and Non-Vasculitic Acute Kidney Injury
by Fatih Yıldırım, Samet Mutlu, Merve Sam Ozdemir, Melek Yalcin Mutlu, Alp Temiz, Sena Tolu, Gamze Akkuzu, Duygu Sevinc Ozgur, Bilgin Karaalioglu, Rabia Deniz, Gürsel Yıldız and Cemal Bes
J. Clin. Med. 2026, 15(3), 1122; https://doi.org/10.3390/jcm15031122 - 31 Jan 2026
Viewed by 142
Abstract
Background/Objectives: Early identification of vasculitic acute kidney injury (AKI) is crucial for timely immunosuppression and improved renal outcomes; however, noninvasive adjunctive diagnostic tools remain limited. Renal elastography, a noninvasive technique that quantifies renal cortical stiffness, has been primarily investigated in chronic kidney disease, [...] Read more.
Background/Objectives: Early identification of vasculitic acute kidney injury (AKI) is crucial for timely immunosuppression and improved renal outcomes; however, noninvasive adjunctive diagnostic tools remain limited. Renal elastography, a noninvasive technique that quantifies renal cortical stiffness, has been primarily investigated in chronic kidney disease, whereas evidence in acute kidney injury is scarce. This study aimed to evaluate the diagnostic utility of renal shear wave elastography for differentiating vasculitic from non-vasculitic AKI and to explore the association between baseline renal cortical stiffness and vasculitic renal outcomes. Materials and Methods: This prospective observational study included three groups: vasculitic AKI, non-vasculitic AKI, and healthy controls. Renal cortical stiffness was measured at admission using two-dimensional shear-wave elastography (2D-SWE) by radiologists blinded to clinical information. After clinicopathological confirmation of definitive diagnoses, between-group comparisons were performed and the diagnostic performance of elastography was evaluated. Additionally, in a biopsy-confirmed immunoglobulin A vasculitis nephritis (IgAVN) cohort (n = 12), baseline elastography measurements were examined in relation to one-year renal outcomes to explore potential prognostic associations. Results: The vasculitic AKI group exhibited significantly higher mean renal cortical stiffness values (9.5 ± 1.9 kPa) compared with both healthy controls (5.53 ± 0.92 kPa) and the non-vasculitic AKI group (6.61 ± 1.89 kPa) (both p < 0.01). Mean renal cortical stiffness demonstrated good diagnostic performance for distinguishing vasculitic from non-vasculitic AKI (AUC 0.86, 95% CI 0.73–0.97), with an optimal threshold of 6.79 kPa yielding 91% sensitivity and 72% specificity. In the prospective one-year follow-up of the IgAVN subcohort (n = 12), patients with unfavorable renal outcomes tended to have higher baseline renal cortical stiffness compared with those with favorable outcomes [median (min–max), 11.2 (10.8–13.3) vs. 9.1 (5.6–11.2), p = 0.046]. Conclusions: These findings suggest that renal elastography may aid in distinguishing vasculitic from non-vasculitic acute kidney injury and may provide exploratory information on the relationship between baseline cortical stiffness and renal outcomes in IgAVN. Full article
(This article belongs to the Section Immunology & Rheumatology)
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23 pages, 1011 KB  
Article
PD-L1/CD274 and miR-155/MIR155HG Genetic Variants as Prognostic and Risk Biomarkers in Diffuse Large B-Cell Lymphoma
by Marija Elez, Debora Misic, Gordana Velikic, Jelena Karajovic, Lavinika Atanaskovic and Gordana Supic
Cancers 2026, 18(3), 469; https://doi.org/10.3390/cancers18030469 - 30 Jan 2026
Viewed by 103
Abstract
Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous malignancy, for which predicting clinical outcomes remains challenging. Although immune-checkpoint pathways are known to influence tumor biology, the impact of their germline variants on DLBCL susceptibility and prognosis has not been [...] Read more.
Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous malignancy, for which predicting clinical outcomes remains challenging. Although immune-checkpoint pathways are known to influence tumor biology, the impact of their germline variants on DLBCL susceptibility and prognosis has not been fully elucidated. Methods: Variants in PD-L1 gene CD274 (rs4143815, rs822336), and miR-155 gene MIR155HG (rs767649, rs1893650), assessed by TaqMan assays in 99 DLBCL patients and 113 age- and sex-matched healthy controls, were associated with clinicopathological features, treatment response, overall survival (OS), relapse-free survival (RFS), and disease susceptibility. Results: The PD-L1 variant rs822336 was significantly associated with relapse status (p = 0.005) and RFS (p = 0.008), with the wild-type GG genotype showing the poorest RFS that remained independent in the multivariate Cox analysis (HR = 2.387, p = 0.003). Conversely, rs4143815 showed a nominal association with treatment resistance (p = 0.026), while patients carrying the GG genotype had worse OS (p = 0.006). In susceptibility analyses, miR-155 variant rs767649 showed a nominal association with DLBCL risk, with the rare AA genotype showing an increased risk of DLBCL (OR = 5.234, p = 0.045), which did not remain significant after Bonferroni correction. Conclusions: In a hypothesis-generating manner, these findings suggest that PD-L1 genetic variants may predominantly influence disease progression and outcomes, while miR-155 variation may contribute to DLBCL susceptibility. These findings highlight germline immunogenetic variants as stable, treatment-independent markers that may inform future studies on risk stratification and prognosis in DLBCL. Full article
(This article belongs to the Special Issue Advances in B-Cell Lymphoma: From Diagnostics to Cure)
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13 pages, 337 KB  
Article
Adverse Histopathological Features in Colorectal Cancer Associated with KRAS rs61764370 SNP: A Preliminary Study
by Tradian Ciprian Berisha, Mihai Gabriel Cucu, Alexandru Calotă-Dobrescu, Simona Serban Sosoi, Ana-Maria Ciurea, Alina Maria Mehedințeanu, Puiu Olivian Stovicek, Ramona Adriana Schenker, Cecil Sorin Mirea, Monica-Laura Cara, Florin Burada and Michael Schenker
Biomedicines 2026, 14(2), 319; https://doi.org/10.3390/biomedicines14020319 - 30 Jan 2026
Viewed by 119
Abstract
Background/Objectives: The KRAS rs61764370 T>G single-nucleotide polymorphism (SNP), located in a let-7 microRNA binding site within the 3′ untranslated region (3′UTR) of the KRAS gene, may modulate tumor aggressiveness by altering post-transcriptional gene regulation. This study evaluated its association with adverse histopathological [...] Read more.
Background/Objectives: The KRAS rs61764370 T>G single-nucleotide polymorphism (SNP), located in a let-7 microRNA binding site within the 3′ untranslated region (3′UTR) of the KRAS gene, may modulate tumor aggressiveness by altering post-transcriptional gene regulation. This study evaluated its association with adverse histopathological features in colorectal cancer (CRC). Methods: A preliminary study on 83 CRC patients carrying either the TT (wild-type, n = 64) or TG (heterozygous, n = 19) genotype was analyzed. Clinicopathological variables included patient sex, tumor location, American Joint Committee on Cancer (AJCC) staging system, histological grade, perineural invasion (PNI), and lymphovascular invasion (LVI). A composite “tumor aggressiveness” score was defined based on the presence of Grade 3 differentiation, LVI, and/or PNI. Group comparisons were performed using the Chi-square test or Fisher’s exact test, as appropriate. Results: No statistically significant differences were observed in sex (p = 0.689), tumor location (p = 0.781), or stage at diagnosis (p = 0.812). Poorly differentiated tumors (Grade 3) were present in 20.3% of TT patients and absent in TG carriers (p = 0.06), while low-grade tumors (Grade 1) were more prevalent among TG patients (47.4%) compared to TT (29.7%). The composite high-aggressiveness score was lower in TG (36.8%) than in TT (48.4%), while co-occurrence of PNI and LVI was similar in both groups (~26%). Conclusions: Although no significant associations were identified, TG carriers showed a tendency toward lower-grade, less aggressive tumors. Given the limited sample size, these findings should be interpreted with caution, necessitating larger cohorts in order to validate results. Full article
14 pages, 1265 KB  
Article
Prognostic Value of Qualitative Splenic [18F]FDG Uptake on Baseline PET/CT in Newly Diagnosed Diffuse Large B-Cell Lymphoma
by Yunhwi Hwang, Sung Hwa Bae, Sang Jun Byun and Byungwook Choi
Cancers 2026, 18(3), 449; https://doi.org/10.3390/cancers18030449 - 30 Jan 2026
Viewed by 84
Abstract
Background/Objectives: Accurate risk stratification at diagnosis is crucial for the optimal management of diffuse large B-cell lymphoma (DLBCL). While Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) is the standard imaging modality for staging, the prognostic value of non-tumoral uptake [...] Read more.
Background/Objectives: Accurate risk stratification at diagnosis is crucial for the optimal management of diffuse large B-cell lymphoma (DLBCL). While Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) is the standard imaging modality for staging, the prognostic value of non-tumoral uptake patterns remains under investigation. Here, we aimed to investigate the prognostic significance of qualitative splenic [18F]FDG uptake on baseline PET/CT in patients with newly diagnosed DLBCL, focusing on relapse-free survival (RFS) and overall survival (OS). Methods: This retrospective study included consecutive patients with newly diagnosed DLBCL in a Korean cohort who underwent baseline [18F]FDG PET/CT between December 2016 and August 2023. Qualitative splenic uptake was visually assessed on maximum intensity projection images. Associations between splenic uptake, prognostic indices, and clinicopathologic characteristics were evaluated. Survival outcomes and independent prognostic factors were analyzed using Kaplan–Meier methods and Cox proportional hazards regression models. Results: A total of 142 patients were analyzed (43 relapsed, 58 died). Positive splenic [18F]FDG uptake was observed in 72 patients and was significantly more frequent in patients who relapsed (p < 0.001). Positive splenic uptake was significantly associated with inferior RFS (p < 0.001) and OS (p = 0.010). For RFS, advanced Ann Arbor stage, ECOG performance status, and extranodal involvement were also significant factors. In multivariable analysis, positive splenic uptake remained an independent predictor of poorer RFS (hazard ratio 2.175, p = 0.043), along with advanced stage (hazard ratio 2.872, p = 0.004). Conclusions: Qualitative splenic [18F]FDG uptake on baseline PET/CT is associated with adverse clinical outcomes in patients with DLBCL and serves as an independent prognostic factor for RFS. Full article
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12 pages, 349 KB  
Article
Endometrial Mixed and Mixed-Feature Carcinomas: Small Cohort Clinicopathologic and Molecular Studies
by Swati Bhardwaj, Mona Saleh, Yayoi Kinoshita, Rachel Brody, Olga Lukatskaya, Stephanie V. Blank, Brett Baskovich and Tamara Kalir
Cancers 2026, 18(3), 440; https://doi.org/10.3390/cancers18030440 - 29 Jan 2026
Viewed by 134
Abstract
Objectives: To examine the clinical, pathologic, and molecular features of mixed and mixed feature endometrial carcinomas and compare them to pure serous carcinoma and pure endometrioid carcinoma. Methods: The study analyzed the clinical characteristics, histologic composition, and molecular genetic profiles of mixed and [...] Read more.
Objectives: To examine the clinical, pathologic, and molecular features of mixed and mixed feature endometrial carcinomas and compare them to pure serous carcinoma and pure endometrioid carcinoma. Methods: The study analyzed the clinical characteristics, histologic composition, and molecular genetic profiles of mixed and mixed feature endometrial cancers, with a focus on shared and distinct mutations. Patient demographics, disease-free survival, and molecular alterations, including in TP53, PIK3CA, TERT, MAP2K1 genes, and ERBB2 gene amplifications, were assessed and compared to pure serous and pure endometrioid carcinomas. Results: Patients with mixed and mixed-feature carcinomas were older (median age: 73 years) and had worse disease-free survival (median: 23 months) than those with pure endometrioid carcinoma (median: 48 months). Mixed and mixed-feature carcinomas were histologically high-grade, most commonly comprising serous and endometrioid components. Molecular profiling supported a clonal origin of these tumors, with identical TP53 and PIK3CA gene mutations between the two histologic components in each case. There were additional gene mutations (e.g., TERT and MAP2K1) found in higher-grade components. ERBB2 amplifications were more frequent in the mixed carcinomas groups (33%) compared to pure serous (11%) and pure endometrioid carcinomas (0%). Some of the mixed and mixed-feature carcinomas also showed FBXW7 mutations, not seen in either the pure endometrioid or pure serous carcinomas. Conclusions: Mixed and mixed-feature carcinomas share origins with pure endometrial serous and endometrioid carcinoma subtypes but exhibit distinct molecular alterations. These findings highlight the importance of molecular subtyping for diagnosis and treatment planning. Future research could focus on larger cohorts and targeted sequencing to better understand the pathogenesis of mixed and mixed-feature carcinomas in order to refine therapeutic strategies. Full article
(This article belongs to the Special Issue Biomarkers for Gynecological Cancers)
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14 pages, 823 KB  
Review
Genomic Subtypes and Computational Biomarkers in Non-Muscle-Invasive Bladder Cancer Guiding Optimal Timing of Radical Cystectomy and BCG Response Prediction
by Vlad-Horia Schițcu, Vlad Cristian Munteanu, Mihnea Bogdan Borz, Ion Cojocaru, Octavia Morari, Mircea Gîrbovan and Andrei-Ionuț Tișe
Genes 2026, 17(2), 153; https://doi.org/10.3390/genes17020153 - 29 Jan 2026
Viewed by 188
Abstract
Non-muscle-invasive bladder cancer (NMIBC) accounts for approximately 70% of newly diagnosed bladder cancer cases but exhibits significant clinical heterogeneity in treatment response and progression risk. While intravesical bacillus Calmette–GuérinCa (BCG) therapy remains the gold standard for high-risk disease, approximately 30–50% of patients experience [...] Read more.
Non-muscle-invasive bladder cancer (NMIBC) accounts for approximately 70% of newly diagnosed bladder cancer cases but exhibits significant clinical heterogeneity in treatment response and progression risk. While intravesical bacillus Calmette–GuérinCa (BCG) therapy remains the gold standard for high-risk disease, approximately 30–50% of patients experience BCG failure, creating a critical decision point between additional bladder-sparing therapy (BST) and early radical cystectomy (RC). Recent clinical data from the CISTO study suggest that, in appropriately selected patients, RC may be associated with higher 12-month recurrence-free survival while maintaining comparable cancer-specific survival and physical functioning. In this narrative review, we synthesize contemporary evidence on NMIBC genomic and transcriptomic subtypes, immune contexture, and clinicopathologic features associated with BCG response and progression risk, with emphasis on clinically oriented classification systems such as BCG Response Subtypes (BRS1–3) and UROMOL21. We highlight how tumor-intrinsic biology (e.g., EMT-associated programs), immune phenotypes (inflamed vs. immune-cold microenvironments), and genomic alterations may help refine risk stratification beyond traditional clinicopathologic models. To facilitate clinical integration, we propose a conceptual decisional framework that combines molecular subtype assignment, immune profiling, key pathologic risk factors, and patient considerations to generate probabilistic risk tiers that support selection among early RC, BST, and clinical trial strategies. Standardized multicenter cohorts and prospective evaluation are needed to validate integrated models and define their clinical utility for the precision timing of cystectomy in BCG-unresponsive NMIBC. Full article
(This article belongs to the Special Issue Computational Genomics and Bioinformatics of Cancer)
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19 pages, 310 KB  
Review
Detecting Occult Sentinel Node Metastases in HNSCC: The Emerging Role of lncRNAs as Biomarkers and Future Perspectives for USgFNAB Molecular Profiling
by Boštjan Lanišnik, Janez Mohorko and Uroš Potočnik
Cancers 2026, 18(3), 427; https://doi.org/10.3390/cancers18030427 - 28 Jan 2026
Viewed by 121
Abstract
Background: Accurate detection of cervical lymph node metastases is a critical determinant of prognosis and treatment planning in head and neck squamous cell carcinoma (HNSCC). Although ultrasound-guided fine-needle aspiration biopsy (USgFNAB) is widely used as a minimally invasive diagnostic tool, its sensitivity [...] Read more.
Background: Accurate detection of cervical lymph node metastases is a critical determinant of prognosis and treatment planning in head and neck squamous cell carcinoma (HNSCC). Although ultrasound-guided fine-needle aspiration biopsy (USgFNAB) is widely used as a minimally invasive diagnostic tool, its sensitivity for detecting occult metastases remains limited. Current preoperative staging modalities are further constrained by operator dependency and suboptimal specificity in early-stage disease. Integration of molecular diagnostics, particularly the analysis of long non-coding RNAs (lncRNAs), represents a promising strategy to enhance diagnostic accuracy. Objective: This review synthesizes the current evidence on lncRNA expression profiles in HNSCC, with an emphasis on their association with lymph node metastasis and potential application in FNAB-derived material for pre-treatment staging. Methods: A structured literature search was conducted, focusing on studies evaluating lncRNA expression profiles in HNSCC and their relevance to lymph node metastasis, with a particular focus on the feasibility of analysis of USgFNAB samples. Results: Multiple lncRNAs, including HOTAIR, MALAT1, UCA1, TUG1, AFAP1-AS1, H19, MEG3, and ADAMTS9-AS2, have been implicated in metastatic progression through their involvement in diverse mechanisms such as epithelial-to-mesenchymal transition, chromatin remodeling, angiogenesis, and pre-metastatic niche formation. Elevated expression of several of these transcripts correlates with adverse clinicopathological features, including advanced tumor stage, extranodal extension, and reduced survival. However, no studies have profiled lncRNA expression in matched primary tumors and metastatic lymph nodes, and transcriptomic analysis of FNAB samples remains largely unexplored in HNSCC. Conclusions: lncRNAs represent promising molecular biomarkers for enhancing the sensitivity and specificity of USgFNAB in detecting occult cervical metastases. Future research should prioritize paired tumor–node lncRNA profiling, validation of FNAB-based molecular assays, and integration of multi-omics data for predictive modeling. Overall, integrating lncRNA analysis into ultrasound-guided fine-needle aspiration biopsy may enhance the detection of occult nodal metastases in head and neck squamous cell carcinoma and support more accurate nodal staging in clinically node-negative patients. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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10 pages, 2736 KB  
Article
Cobblestone-like Gastric Mucosal Changes on Endoscopy in Dogs with a History of Prolonged Proton Pump Inhibitor Therapy
by Martine Dominique Didier, Laura Zagnoli, Deborah Cattaneo, Silvia Lucia Benali and Enrico Bottero
Animals 2026, 16(3), 406; https://doi.org/10.3390/ani16030406 - 28 Jan 2026
Viewed by 133
Abstract
This study describes the clinicopathological features of seven canine cases showing a diffuse cobblestone-like gastric mucosal pattern on endoscopy. Cases were retrospectively retrieved from endoscopic databases (2017–2025). Clinical data, treatment history, endoscopic findings, and histology were reviewed. Endoscopically, all dogs exhibited thickened, irregular, [...] Read more.
This study describes the clinicopathological features of seven canine cases showing a diffuse cobblestone-like gastric mucosal pattern on endoscopy. Cases were retrospectively retrieved from endoscopic databases (2017–2025). Clinical data, treatment history, endoscopic findings, and histology were reviewed. Endoscopically, all dogs exhibited thickened, irregular, and poorly distensible gastric folds. Histopathologic examination showed mild-to-moderate foveolar hyperplasia, variable cystic dilation of the fundic glands, mild chronic lymphoplasmacytic inflammation, and interstitial fibrosis. Parietal-cell population was variably increased and predominant (hyperplasia). Because these features can overlap widely among reactive and hyperplastic gastropathies, interpretation required correlation with clinical and endoscopic findings in addition to histopathology. All dogs had a history of prolonged omeprazole administration, and most showed clinical improvement after dose reduction or treatment withdrawal. Follow-up endoscopy in two dogs documented divergent outcomes, with marked improvement in one dog and only minimal changes in the other. These findings suggest that this cobblestone-like pattern represents a benign, reactive, and potentially regressive gastropathy, possibly associated with chronic acid suppression. Recognition of this appearance may assist clinicians in differentiating reactive gastropathy from proliferative or neoplastic conditions and supports prudent use of long-term proton pump inhibitors in dogs with chronic gastrointestinal disease. Full article
(This article belongs to the Special Issue Endoscopy of Pets)
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11 pages, 747 KB  
Article
Association Between Cribriform Architecture and Lymphovascular Invasion in Prostate Cancer
by Jacqueline Chan, Yetkin Tuac, Okan Argun, Christina M. Breneman, Nora Seeley, Haley N. Moriarty, Keerthana Senthil Kumar, Fallon E. Chipidza, Jonathan E. Leeman and Mutlay Sayan
J. Clin. Med. 2026, 15(3), 1032; https://doi.org/10.3390/jcm15031032 - 28 Jan 2026
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Abstract
Background/Objectives: Cribriform architecture is an adverse histopathologic feature in prostate cancer and has been associated with poor oncologic outcomes. Emerging evidence suggests that cribriform-positive tumors may behave as a biologically non-localized disease, raising the possibility of early occult dissemination. Lymphovascular invasion (LVI) is [...] Read more.
Background/Objectives: Cribriform architecture is an adverse histopathologic feature in prostate cancer and has been associated with poor oncologic outcomes. Emerging evidence suggests that cribriform-positive tumors may behave as a biologically non-localized disease, raising the possibility of early occult dissemination. Lymphovascular invasion (LVI) is a key pathological marker of metastatic potential, but its relationship with cribriform architecture has not been evaluated. We examined the association between cribriform morphology and LVI to provide biological context for the aggressive clinical course of cribriform-positive prostate cancer. Methods: We performed a retrospective analysis of patients with prostate adenocarcinoma who underwent radical prostatectomy and had available clinicopathologic data. Cribriform architecture was determined by a centralized pathology review, and LVI status was obtained from original pathology reports. Unadjusted associations were evaluated using contingency tables. Multivariable logistic regression was used to assess whether cribriform architecture was independently associated with LVI after adjustments for Gleason score, tumor stage, and nodal status. Results: Among 338 patients, 28 (8.3%) had LVI and 123 (36.4%) had cribriform architecture. LVI was more common in cribriform-positive than cribriform-negative tumors (17.9% vs. 2.8%; p < 0.001), corresponding to a crude odds ratio (OR) of 7.6 (95% CI, 3.0–19.3). Cribriform architecture remained independently associated with LVI after adjustment (adjusted OR, 5.20; 95% CI, 2.12–1.40; p < 0.001). Conclusions: Cribriform architecture is strongly and independently associated with LVI, supporting a biological link between cribriform morphology and early metastatic dissemination. These findings support the design of prospective, biomarker-driven studies to evaluate treatment intensification strategies in this high-risk subgroup. Full article
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25 pages, 3087 KB  
Article
Tumor-Associated Neutrophils and Desmoplastic Reaction in Breast Cancer Microenvironment: Association with Tumor Grade and Clinicopathological Features
by Stavroula Papadopoulou, Vasiliki Michou, Arsenios Tsiotsias, Maria Tzitiridou-Chatzopoulou and Panagiotis Eskitzis
Cancers 2026, 18(3), 406; https://doi.org/10.3390/cancers18030406 - 27 Jan 2026
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Abstract
Background: The tumor microenvironment (TME), composed of diverse immune and stromal cells, plays a key role in cancer progression. Among its components, tumor-associated neutrophils (TANs) and the desmoplastic reaction (DR) have emerged as important modulators of tumor behavior. While each has been extensively [...] Read more.
Background: The tumor microenvironment (TME), composed of diverse immune and stromal cells, plays a key role in cancer progression. Among its components, tumor-associated neutrophils (TANs) and the desmoplastic reaction (DR) have emerged as important modulators of tumor behavior. While each has been extensively studied, their interrelationship and association with tumor grade and clinicopathological parameters remain unclear. Aim: This hypothesis-generating study aimed to explore the relationship between the presence of TANs, various types of DR, the grade of tumor malignancy, and other fundamental clinicopathological characteristics commonly studied in daily clinical practice. Materials and Methods: The study included a cohort of 65 cancer patients (N = 65). The average number of TANs was recorded. In hematoxylin and eosin (H&E)-stained sections, “hot spots” representing areas with the highest neutrophil density were first identified. The tumor-associated polymorphonuclear neutrophils were then counted in ten consecutive high-power fields (HPFs). In the same specimens, the DR was assessed and classified according to stromal texture. Results: TANs did not follow a normal distribution across any clinicopathological category (p < 0.05). Significant differences in TAN levels were observed among DR types (Kruskal–Wallis H = 9.890, p = 0.007), with higher counts in myxoid compared to mature stroma (Mean Rank = 41.58 vs. 24.80, p = 0.006). TAN levels also varied significantly with tumor grade (H = 22.384, p < 0.001), increasing from Grade 1 to Grade 3 (p < 0.013–0.001). Higher TAN counts were associated with cellular erythroblastic oncogene B2 (c-erbB2) positivity (H = 6.547, p = 0.038), perineural invasion (Mann–Whitney U = 179.5, p < 0.001), and ER/PR negativity (p = 0.016 and p = 0.044, respectively). No significant association was found with necrosis (p = 0.083). A near-significant relationship was identified between DR type and tumor differentiation grade (χ2 = 9.448, p = 0.051), with mature stroma most common in Grade 1 tumors, keloid-like stroma in Grade 2, and myxoid stroma in Grade 3. Conclusions: High TAN levels were linked to aggressive tumor features and specific DR patterns. The association of myxoid stroma with elevated TAN infiltration may reflect a highly aggressive TME. These preliminary results warrant validation in larger, prospective studies. Full article
(This article belongs to the Section Tumor Microenvironment)
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