Search Results (929)

Background/Objectives: PROX1 (prospero homeobox 1) is a transcription factor involved in lymphangiogenesis and cellular differentiation. Its role in cancer biology appears to be highly context-dependent, with it exhibiting both tumor-promoting and -suppressive functions across various malignancies. Nonetheless, the clinical significance of PROX1 expression in non-small cell lung cancer (NSCLC) remains poorly elucidated. The objective of this study is to evaluate the immunohistochemical expression of PROX1 in NSCLC, specifically in the adenocarcinoma and squamous cell carcinoma subtypes, and to assess its correlation with clinicopathologic features and overall survival (OS). Methods: This retrospective study included surgically resected specimens from 121 patients with histologically confirmed NSCLC. PROX1 expression was assessed via immunohistochemistry on formalin-fixed, paraffin-embedded specimens. Staining intensity (graded 0– National and Kapodistrian University of Athens 3) and the percentage of positive tumor cells were recorded. Correlations with histological subtype, tumor characteristics, and OS were analyzed using chi-square tests, one-way ANOVA, and Kaplan–Meier survival analysis with log-rank testing. Results: Low PROX1 intensity (level 1) was significantly associated with P63 positivity (p = 0.028), while high PROX1 intensity (level 3) correlated with nodal metastasis to station 3 (S3+) (p = 0.025). Additionally, alveolar-pattern adenocarcinomas exhibited intermediate PROX1 expression (26–50%) (p = 0.010). Although PROX1 positivity did not differ among mucinous and non-mucinous adenocarcinomas (p = 0.152), its distribution across defined expression subgroups was statistically significant (p = 0.002). Tumors with low PROX1 expression (0–24%) were associated with a larger maximum tumor diameter (p = 0.026). PROX1 expression was not independently associated with OS (p > 0.05). Factors significantly associated with improved survival included an age < 50 years, female sex, the absence of necrosis, fewer than 10 positive lymph nodes, a lymph node ratio < 0.5, and the absence of extensive nodal involvement in stations 5, 10, 11, and 12. Conclusions: Although PROX1 expression is variably associated with specific histologic subtypes and nodal metastases in NSCLC, it does not independently predict overall survival. Its expression patterns suggest a potential role in tumor differentiation and lymphatic spread. Further mechanistic and immunologic studies are warranted to elucidate the functional significance of PROX1 in lung cancer biology. Full article

Background/Objectives: Granulomatous lesions of the head and neck arise from diverse infectious and non-infectious causes, with tuberculosis (TB) being a predominant etiology. This retrospective study analyzed 42 cases from the archives of university of Baghdad, College of Dentistry (1975–2025). This study aimed to characterize the clinicopathological features of these lesions and to assess the diagnostic performance of histochemical stains and real-time PCR in identifying infectious etiologies—particularly Mycobacterium tuberculosis—in formalin-fixed, paraffin-embedded (FFPE) tissue samples. Methods: Definitive diagnoses included 25 TB cases confirmed through clinical, microbiological, and therapeutic follow-up at the Baghdad Tuberculosis Institute, and 17 non-TB cases classified by predefined clinicopathological criteria supported by relevant clinical data. Zieh–Neelsen (ZN), Periodic acid–Schiff (PAS), and Grocott methenamine silver (GMS) stains were employed to identify acid-fast bacilli and fungal organisms. Statistical analysis was performed using SPSS version 26, with significance set at p ≤ 0.05. Results: The mean patient age was 36.28 years (SD = 20.6), with a female predominance (59.5%). Necrotizing granulomas were identified in 69% of cases and were strongly associated with tuberculosis, which was detected in 59.5% of specimens. ZN staining showed a sensitivity of 16.7% for tuberculosis, while PCR sensitivity was highly dependent on sample age. The detection rate was 33.3% in samples archived for less than 10 years but only 10% in older samples, resulting in an overall sensitivity of 24.0% for tuberculous cases. Langhans-type giant cells were significantly more frequent in necrotizing granulomas and strongly associated with tuberculosis infection (p = 0.001). Fungal infections, predominantly aspergillosis, were confirmed by PAS and GMS in 11.9% and 9.5% of cases, respectively, and were confined to non-necrotizing granulomas. The mandible was the most commonly affected site, and soft tissue lesions were significantly associated with necrotizing granulomas (p = 0.004). Conclusions: These findings underscore the complementary role of histopathology, histochemical stains, and molecular diagnostics in improving the evaluation and diagnosis of granulomatous inflammation in head and neck lesions. Full article

Background: Thymoma is a malignant tumor originating from the thymic epithelium and can be associated with over 100 paraneoplastic syndromes (PNSs). Due to the low incidence of thymoma and the relative rarity of alopecia areata (AA) as an associated autoimmune disease, patients with thymoma combined with AA are relatively uncommon in clinical practice. As a result, the clinicopathological features and pathogenesis of such patients have been rarely investigated. Methods: This study retrospectively analyzed the clinical records of thymoma patients who underwent surgical treatment at Peking Union Medical College Hospital and Beijing Tongren Hospital from August 2014 to July 2019, with a focus on the clinicopathological features of thymoma patients with AA. Propensity score matching (PSM) was employed to create a 1:5 matched comparison group with thymoma patients without AA. Results: A total of 428 thymoma patients were included, among which 9 had AA. Using PSM, we matched 45 control patients without AA based on age and gender. The analysis revealed that thymoma patients with AA had a significantly higher proportion of myasthenia gravis (MG) [100.00% (9/9) vs. 66.67% (30/45), p = 0.049], although there were no significant differences between the AChR antibodies, Titin antibodies, MG severity, and the incidence of postoperative myasthenic crisis. However, the proportion of thymoma patients with AA who also had other PNSs besides MG was significantly higher [88.89% (8/9) vs. 6.67% (3/45), p < 0.001]. Additionally, CD4⁺/CD8⁺ T-cell inversion in the serum was observed at a much higher rate in thymoma patients with AA [100.00% (9/9) vs. 24.44% (11/45), p < 0.001]. Conclusions: We hypothesize that the pathogenesis of thymoma with AA differs from that of thymoma with MG, though there may be a correlation. The etiology of thymoma with AA may be attributed to abnormal autoimmune CD8⁺ T lymphocytes produced by the thymoma, which can also lead to other cytotoxic T-cell-mediated autoimmune diseases. Full article

Background/Objectives: This study aimed to evaluate the diagnostic performance of simplified intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) parameters in distinguishing malignant from benign breast lesions, and to explore their association with clinicopathological features. Methods: This retrospective study included 108 women who underwent breast MRI with multi-b-value DWI (0, 20, 200, 500, 800 s/mm²). Of those 108 women, 73 had pathologically confirmed malignant lesions. IVIM maps (ADC_map, D, D*, and perfusion fraction f) were generated using IB-Diffusion™ software version 21.12. Lesions were manually segmented by radiologists, and clinicopathological data including receptor status, Ki-67 index, cancer type, histologic grade, and molecular subtype were extracted from medical records. Nonparametric tests and ROC analysis were used to assess group differences and diagnostic performance. Additionally, a binary logistic regression model combining D, D*, and f was developed to evaluate their joint diagnostic utility, with ROC analysis applied to the model’s predicted probabilities. Results: Malignant lesions demonstrated significantly lower diffusion parameters compared to benign lesions, including ADC_map (p = 0.004), D (p = 0.009), and D* (p = 0.016), indicating restricted diffusion in cancerous tissue. In contrast, the perfusion fraction (f) did not show a significant difference (p = 0.202). ROC analysis revealed moderate diagnostic accuracy for ADC_map (AUC = 0.671), D (AUC = 0.657), and D* (AUC = 0.644), while f showed poor discrimination (AUC = 0.576, p = 0.186). A combined logistic regression model using D, D*, and f significantly improved diagnostic performance, achieving an AUC of 0.725 (p < 0.001), with 67.1% sensitivity and 74.3% specificity. ADC_map achieved the highest sensitivity (100%) but had low specificity (11.4%). Among clinicopathological features, only histologic grade was significantly associated with IVIM metrics, with higher-grade tumors showing lower ADC_map and D* values (p = 0.042 and p = 0.046, respectively). No significant associations were found between IVIM parameters and ER, PR, HER2 status, Ki-67 index, cancer type, or molecular subtype. Conclusions: Simplified IVIM DWI offers moderate accuracy in distinguishing malignant from benign breast lesions, with diffusion-related parameters (ADC_map, D, D*) showing the strongest diagnostic value. Incorporating D, D*, and f into a combined model enhanced diagnostic performance compared to individual IVIM metrics, supporting the potential of multivariate IVIM analysis in breast lesion characterization. Tumor grade was the only clinicopathological feature consistently associated with diffusion metrics, suggesting that IVIM may reflect underlying tumor differentiation but has limited utility for molecular subtype classification. Full article

Neuroendocrine neoplasms (NENs) of the lung are a biologically and clinically diverse group of tumors that includes well-differentiated typical and atypical carcinoids (LNETs), as well as poorly differentiated large-cell neuroendocrine carcinoma and small-cell lung cancer. Despite their relative rarity, the incidence of LNETs is increasing, primarily due to advancements in diagnostic techniques and heightened clinical awareness. While the current World Health Organization (WHO) classification offers a morphological basis for diagnosis and prognosis, particularly for extrapulmonary neuroendocrine neoplasms (ep-NENs), it has limitations in predicting the clinical behavior of pulmonary carcinoids. Recent evidence highlights the inadequacy of traditional criteria in fully capturing the biological complexity and clinical heterogeneity of these tumors. This review explores the evolving landscape of LNETs, focusing on well-differentiated forms and analyzing current classification systems, clinicopathological features, and the emerging role of novel prognostic and predictive biomarkers. Advances in histopathology and molecular profiling have begun to elucidate distinct molecular subsets within carcinoids, offering potential avenues for improved risk stratification and therapeutic decision-making. Although there are limited treatment options for advanced disease, new insights into tumor biology could facilitate the development of personalized therapeutic strategies and pave the way for future innovations in LNET management. Full article

Diffuse alimentary lymphoma (AL) in dogs is an under-characterized entity lacking well-defined diagnostic criteria. This retrospective study evaluated the clinical, endoscopic, histopathological, and immunohistochemical features of 18 dogs diagnosed with diffuse AL between 2017 and 2024. The inclusion criteria for dogs were an abdominal ultrasound, gastrointestinal endoscopy with multiple mucosal biopsies, and the availability of both histopathological as well as immunohistochemical data. Dogs with an intestinal mass were excluded. The duodenum was the most frequently affected segment, with a “cobblestone” endoscopic appearance noted in 53% (9/17) of dogs undergoing upper gastrointestinal endoscopy. Compared to dogs without this feature, those with a “cobblestone” appearance of the duodenal mucosa had significantly lower plasma albumin concentrations (mean: 18.8 g/L, SD: 4.32, range: 19–31 vs. mean: 25.3 g/L, SD: 4.3, range: 19–31; p = 0.007), higher CCECAI scores (mean: 11.1, SD: 1.45, range: 9–13 vs. mean: 8.0, SD: 2.27, range: 5–12; p = 0.004), and shorter survival time (median: 9 days, range: 4–58 vs. median: 92 days, range: 12–350; log-rank test: p = 0.02). While certain endoscopic features—such as a “cobblestone” duodenal mucosal appearance—were associated with more severe clinical and biological profiles, the diagnostic value of these lesions remains to be clarified. Full article

Background and Objectives: Total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC) offers significant advantages in terms of pathologic response and long-term survival; however, it is still unclear which patients will benefit the most from this treatment. This study aims to investigate the role of metabolic parameters on pretreatment positron emission tomography–computed tomography (PET/CT) images in predicting treatment response after TNT. Materials and Methods: The research was conducted using a single-center, retrospective design. Patients treated with total neoadjuvant therapy are included if they have locally advanced rectal cancer (cT3/T4-N0 or cTany-N1/N2). The patient group was categorized into two groups: CR and non-CR. Clinicopathologic features, PET/CT parameters, CA19-9, and CEA values were compared between these two groups. Results: In total, 52 patients were included. The CR group had 21 patients, and the non-CR group had 31 patients. The analysis demonstrated that the CR group had significantly lower metabolic tumor volume (MTV) and total lesion glycolysis (TLG) than the non-CR group (p = 0.022 vs. p = 0.003, p < 0.05). Also, CA19-9 values were lower than the non-CR group, and this difference was statistically remarkable (p = 0.40, p < 0.05). Conclusions: MTV and TLG parameters in PET/CT for pretreatment staging and pretreatment blood CA 19-9 levels are prognostic factors for predicting treatment response, and they may play a crucial role in choosing treatment. Comprehensive research is warranted on this subject with a larger patient population. Full article

High-risk prostate cancer (PC) accounts for 50–75% of 10-year relapse after primary treatment. Routine clinicopathological parameters for PC patient stratification have proven insufficient to inform clinical decisions in this setting. Tumor genomic profiling allowed overcoming the limits of diagnostic accuracy in the field of PC, integrated with radiomic features, automated platforms, evaluation of patient-related factors (age, performance status, comorbidity) and tumor-related factors (risk class, volume, T stage). In this scenario, the use of biomarkers to guide decision-making in localized, high-risk PC is evolving actively and rapidly. Additional tests for prostate-specific antigen have demonstrated superior sensitivity and specificity for detecting clinically significant PC, as well as commercially available genomic classifiers improving the risk prediction of disease recurrence/progression/metastasis, in combination with common clinical variables. This narrative review aimed to summarize the state of the art on the utility and evolution of old and emerging biomarkers in the diagnosis and prognosis of localized, high-risk PC, and the potential for their application in clinical practice. We focused on the theoretical molecular foundation of prostate carcinogenesis and explored the impact of genomic profiling, next-generation sequencing, and artificial intelligence in the extrapolation of customized features able to predict disease aggressiveness and possibly drive personalized therapeutic decisions. Full article

As obesity and Western diet consumption are key factors contributing to gut dysbiosis, we investigated the relationship between intestinal microbiota, obesity, and psoriasis in an imiquimod-based model. C57BL/6 mice were used as follows: psoriasis-induced groups fed continuously with a standard or Western diet, psoriasis-induced group fed with a Western diet and then returned to a standard diet, and controls. For each group, clinicopathological, immune, and metabolic parameters were integrated with microbiome data. The imiquimod-based models displayed human psoriasis features and significant changes in immune parameters. Hence, psoriatic mice on prolonged high-fat intake presented decreased microbial richness and evenness and a gut microbiome composition resembling that of obese mice. Ruminococcus, Clostridium, Desulfovibrio, and Enterorhabdus were the most abundant genera in the obesity-enhanced psoriasis group. Raoultella abundance was linked with psoriasis. Yet, the same pathobionts over-represented in the obese psoriatic mice displayed positive correlations with metabolic stress indicators and proinflammatory factors, indicating potential biomarkers of disease severity. Conversely, Lactobacillus taiwanensis, Alistipes putredinis, and Eubacterium hadrum might be potential taxa for attenuating the metabolic burden in obesity-enhanced psoriasis. Here, we depict the microbial signatures associated with inflammation and metabolic stress in an obesity-aggravated psoriasis mouse model. Full article

Background: Papillary thyroid microcarcinoma (PTMC) is associated with certain features that carry an increased risk of local recurrence, underscoring the importance of preoperative risk assessment. This study investigated the clinicopathological factors associated with high-risk lymph node metastasis (HRLNM) and patient outcomes. HRLNM is defined as ≥5 metastatic lymph nodes and/or lateral neck metastasis. Methods: We conducted a retrospective review of 985 patients with PTMC who underwent thyroidectomy at the Kaohsiung Chang Gung Memorial Hospital from 2013 to 2022. Results: Among the 985 patients, 100 (10.2%) had lymph node metastasis (LNM), and 27% of these were classified as having HRLNM. Male sex (OR 3.61, p = 0.04) and extranodal extension (OR 3.76, p = 0.043) were independent predictors of HRLNM. Patients with LNM exhibited lower rates of excellent treatment response (75% vs. 87%, p = 0.001), higher recurrence rates (9.0% vs. 0.6%, p = 0.001), and an increased risk of distant metastasis (2.0% vs. 0%). Recurrence-free survival (RFS) was significantly shorter in patients with LNM (120.9 vs. 198.6 months, p < 0.001). Although HRLNM showed a trend toward reduced RFS (113.5 vs. 124.6 months, p = 0.177), its impact on long-term survival remains uncertain. Conclusions: Male sex and extranodal extension were significant risk factors for HRLNM in patients with PTMC. These findings highlight the need for individualized risk stratification to guide treatment strategies and improve patient outcomes. Full article

Gastric-type cervical adenocarcinoma (GCA) is a rare and aggressive subtype of cervical adenocarcinoma. Despite its clinical significance, its molecular carcinogenesis and therapeutic targets remain poorly understood. This study aimed to compare the clinicopathological, immunohistochemical, and molecular profiles of GCA and usual-type cervical adenocarcinoma (UCA), exploring prognostic and therapeutic biomarkers in a Japanese population. A total of 110 cervical adenocarcinoma cases, including 16 GCA and 94 UCA cases, were retrospectively analyzed for clinicopathological features, and a panel of immunohistochemical markers was assessed. Sanger sequences were performed for the KRAS, PIK3CA, and BRAF genes, and survival and clinicopathological correlations were assessed using Kaplan–Meier and Cox regression analyses. GCA was significantly associated with more aggressive features than UCA, including lymph node involvement, advanced FIGO stages, increasing recurrence rate, and poor survival status. High ARID1B expression was observed in a subset of GCA cases and correlated with worse progression-free and overall survival. Additionally, PD-L1 expression was more frequent in GCA than UCA and was associated with unfavorable prognostic factors. Conversely, UCA cases showed strong p16 expression, supporting their HPV-driven pathogenesis. Molecular profiling revealed KRAS and PIK3CA mutations in both subtypes, while BRAF mutations were identified exclusively in GCA. These findings reveal distinct clinical and molecular profiles for both tumor types and underscore ARID1B and PD-L1 as predictive prognostic and therapeutic biomarkers in GCA, implicating the use of subtype-specific treatment strategies. Full article

Triple-negative breast cancer (TNBC) is a clinically and molecularly heterogeneous subtype defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. In this study, tumor specimens from 104 TNBC patients were analyzed to characterize molecular and clinicopathological features and to assess the expression and therapeutic potential of four key surface markers: epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCAM), tissue factor (TF), and trophoblast cell surface antigen (TROP2). Multiplex immunofluorescence (mIF) demonstrated elevated EGFR and TROP2 expression in the majority of samples. Significant positive correlations were observed between EGFR and TF, as well as between TROP2 and both TF and EpCAM. Expression analyses revealed increased EGFR and TF levels with advancing tumor stage, whereas EpCAM expression declined in advanced-stage tumors. TROP2 and TF expression were significantly elevated in higher-grade tumors. Additionally, EGFR and EpCAM levels were significantly higher in patients with elevated Ki-67 indices. Binding specificity assays using single-chain variable fragment (scFv-SNAP) fusion proteins confirmed robust targeting efficacy, particularly for EGFR and TROP2. These findings underscore the therapeutic relevance of EGFR and TROP2 as potential biomarkers and targets in TNBC. Full article

Background/Objectives: Delayed gastric emptying (DGE) is a well-known complication of laparoscopic pylorus-preserving gastrectomy (LPPG). Patients who underwent LPPG in the KLASS-04 trial, which was a multicenter prospective randomized control trial comparing LPPG and laparoscopic distal gastrectomy (LDG), showed an unneglectable incidence of long-term DGE compared to patients who underwent LDG. This study aimed to identify the multifactorial risk factors associated with DGE and to analyze the quality of life (QoL) of patients with DGE following LPPG. Methods: DGE was defined as “nearly normal diet residue” at least once in the endoscopic follow-up at 1, 2, and 3 years after the surgery. Clinicopathological features, surgical outcomes, and QoL were compared between the DGE and non-DGE groups. Results: DGE was observed in 21/124 patients (16.3%) who underwent LPPG. Patients without previous abdominal surgery had a higher incidence of DGE in the univariate (32% vs. 4.8%, p = 0.011) and logistic regression analyses (odds ratio: 0.106, 95% confidence interval: 0.014–0.824, p = 0.032). Patients with DGE reported more symptoms of nausea and vomiting (p = 0.004), constipation (p = 0.04), and a dry mouth (p = 0.005). Conclusions: Despite the strict protocol used to avoid well-known risk factors for DGE, such as damage to the hepatic branch of the vagus nerve, infrapyloric artery and vein, and short antral cuff, the LPPG group of the KLASS-04 trial exhibited a considerable incidence of DGE. No clinicopathological or surgical factors, other than the absence of a previous surgical history, were identified as multifactorial risk factors for DGE. However, DGE had a negative impact on the QoL of patients. Full article

Background/Objectives: To develop a DL-based model predicting recurrence risk in HER2-low breast cancer patients and to compare performance of the MRI-alone, clinicopathologic-alone, and combined models. Methods: We analyzed 453 patients with HER2-low breast cancer who underwent surgery and preoperative breast MRI between May 2018 and April 2022. Patients were randomly assigned to either a training cohort (n = 331) or a test cohort (n = 122). Imaging features were extracted from DCE-MRI and ADC maps, with regions of interest manually annotated by radiologists. Clinicopathological features included tumor size, nodal status, histological grade, and hormone receptor status. Three DL prediction models were developed: a CNN-based MRI-alone model, a clinicopathologic-alone model based on a multi-layer perceptron (MLP) and a combined model integrating CNN-extracted MRI features with clinicopathological data via MLP. Model performance was evaluated using AUC, sensitivity, specificity, and F1-score. Results: The MRI-alone model achieved an AUC of 0.69 (95% CI, 0.68–0.69), with a sensitivity of 37.6% (95% CI, 35.7–39.4), specificity of 87.5% (95% CI, 86.9–88.2), and F1-score of 0.34 (95% CI, 0.33–0.35). The clinicopathologic-alone model yielded the highest AUC of 0.92 (95% CI, 0.92–0.92) and sensitivity of 93.6% (95% CI, 93.4–93.8), but showed the lowest specificity (72.3%, 95% CI, 71.8–72.8) and F1-score of 0.50 (95% CI, 0.49–0.50). The combined model demonstrated the most balanced performance, achieving an AUC of 0.90 (95% CI, 0.89–0.91), sensitivity of 80.0% (95% CI, 78.7–81.3), specificity of 83.2% (95% CI: 82.7–83.6), and the highest F1-score of 0.55 (95% CI, 0.54–0.57). Conclusions: The DL-based model combining MRI and clinicopathological features showed superior performance in predicting recurrence in HER2-low breast cancer. This multimodal approach offers a framework for individualized risk assessment and may aid in refining follow-up strategies. Full article

Background: Gastric cancer (GC) represents a significant global health burden with considerable heterogeneity in clinical and molecular behavior. The anatomical site of tumor origin—proximal versus distal—has emerged as a determinant of prognosis and response to therapy. The aim of this paper is to elucidate the transcriptional and regulatory differences between proximal gastric cancer (PGC) and distal gastric cancer (DGC) through master regulator (MR) analysis. Methods: We analyzed RNA-seq data from TCGA-STAD and microarray data from GEO (GSE62254, GSE15459). Differential gene expression and MR analyses were performed using DESeq2, limma, corto, and RegEnrich pipelines. A harmonized matrix of 4785 genes was used for MR inference following normalization and batch correction. Functional enrichment and survival analyses were conducted to explore prognostic associations. Results: Among 364 TCGA and 492 GEO patients, PGC was associated with more aggressive clinicopathological features and poorer outcomes. We identified 998 DEGs distinguishing PGC and DGC. PGC showed increased FOXM1 (a key regulator of cell proliferation), STAT3, and NF-κB1 activity, while DGC displayed enriched GATA6, CDX2 (a marker of intestinal differentiation), and HNF4A signaling. Functional enrichment highlighted proliferative and inflammatory programs in PGC, and differentiation and metabolic pathways in DGC. MR activity stratified survival outcomes, reinforcing prognostic relevance. Conclusions: PGC and DGC are governed by distinct transcriptional regulators and signaling networks. Our findings provide a biological rationale for location-based stratification and inform targeted therapy development. Full article