Search Results (920)

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

Lacrimal cysts (dacryops), which involve lacrimal tissue, are uncommon in dogs with an obscure/unclear pathogenesis. Compared to the current available literature, this report describes the clinicopathologic and immunohistochemical features of two cases of unusual dacryops in brachycephalic dogs. A three-year-old male Cane Corso was referred with a 1-month history of swelling ventromedial to the left eye associated with blepharospasm and epiphora. Furthermore, a severe lower and upper eyelid entropion and a deep corneal ulcer were present. B-mode ultrasonography and a CT scan revealed a subcutaneous cyst, closely adherent to the maxillary bone. Surgical removal and the correction of entropion were performed. No recurrence and/or complication was detected by seven-year follow-up. Histopathology revealed a cystic structure with single- to double-cell-layered, nonciliated, cuboidal epithelia. Alcian blue stain revealed rare, disseminated goblet cells admixed with epithelial cells. The epithelium was strongly Cytokeratin-positive by immunohistochemistry and appeared lined by several layers of smooth muscle actin (SMA)-positive myoepithelial cells. A 1-year-old male French Bulldog with a 3-month lesion of the third eyelid of the right eye. The lesion (15 mm × 7 mm) beneath the conjunctiva appeared pale-pink, smooth, and multilobulated. Excision was performed by blunt dissection through the conjunctiva on the palpebral surface of the third eyelid. Recovery was uncomplicated, and no recurrence has been noted at three-year follow-up. Cytology of the cystic fluid and histopathology and immunohistochemistry of the cyst wall revealed findings for case 1. To further characterize the SMA-positive spindle cells located directly beneath the cyst-lining epithelium, double-color immunofluorescence for SMA and p63 (a myoepithelial cell marker) was performed on the sample from case 2. The analysis revealed that the SMA-positive cells lacked p63 expression, indicating a non-myoepithelial phenotype. The histological findings in our cases are consistent with previous reports of canine dacryops. The positivity of immunohistochemical staining for SMA in cells directly beneath the epithelium of dacryops in the cases here described in two brachycephalic dogs is consistent with previous reports in dogs and horses but in contrast with a retrospective study about a human dacryops. These results support the conclusion that the pathogenesis of dacryops in dogs should exclude failure of ductular “neuromuscular” contractility. Full article

Background: Peritoneal dissemination in colorectal cancer (CRC) is associated with poor prognosis due to limited efficacy of current therapeutic strategies. The cholinergic receptor nicotinic beta 2 subunit (CHRNB2), a component of the acetylcholine receptor, has been implicated in other malignancies, but its role in CRC remains unknown. Methods: This study evaluated the expression and function of CHRNB2 in CRC. CHRNB2 mRNA levels were quantified by qRT-PCR in cell lines and clinical specimens. Functional assays were conducted using CRC cell lines with high CHRNB2 expression, in which CHRNB2 was knocked down by shRNA. Cell proliferation, migration, and invasion were assessed in vitro. In vivo effects were evaluated using subcutaneous and peritoneal xenograft models. The impact of CHRNB2 monoclonal antibody (mAb) treatment on CRC cell proliferation was also examined. Clinical correlations were assessed between CHRNB2 expression and clinicopathological features, including recurrence patterns. Results: CHRNB2 expression varied among CRC cell lines, with the highest levels observed in LOVO cells. CHRNB2 knockdown significantly inhibited proliferation, migration, and invasion in vitro and suppressed tumor growth in vivo. CHRNB2 mAb treatment reduced cell proliferation. Clinically, high CHRNB2 expression correlated with a significantly higher cumulative rate of peritoneal recurrence, but not with recurrence in the liver, lungs, or lymph nodes. Multivariate analysis identified high CHRNB2 expression and T4 tumor depth as independent predictors of peritoneal recurrence. Conclusions: CHRNB2 promotes the malignant phenotype of CRC, particularly in peritoneal dissemination. These findings suggest that CHRNB2 may serve as a novel diagnostic biomarker and therapeutic target for CRC with peritoneal metastasis. Full article

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

Background: Ovarian clear cell carcinoma (OCCC) is characterized by chemoresistance and poor prognosis in advanced or recurrent cases. This study aimed to find specific prognostic markers for OCCC. Methods: We analyzed 169 OCCC patients for clinicopathological features. TERT promoter and PIK3CA mutations were assessed by Sanger sequencing, and immunohistochemistry for ARID1A, HDAC6, Cyclin E1, and p53 was performed on tissue microarrays. Survival analysis was conducted using Kaplan–Meier and Cox regression models. Results: The -124C>T TERT promoter mutation was associated with longer OS and PFS and was an independent predictor of favorable OS. This mutation correlated with lower CA125 levels and higher SNP frequency. p53 mutations indicated advanced disease, bilateral tumors, reduced Cyclin E1, and poor prognosis. Low HDAC6 expression was linked to worse PFS. Mutual exclusivity was observed between PIK3CA exon 20 mutations and SNPs. Conclusions: The -124C>T TERT promoter mutation may serve as a favorable prognostic marker in OCCC, while p53 mutations and reduced HDAC6 expression are associated with poor outcomes. Full article

Background/Objectives: Endometrial cancer (EC) is the most prevalent gynecological malignancy, with increasing incidence and mortality. HOXA5, a developmental transcription factor, has been linked to prognosis in various cancers, but its role in EC remains unclear. This study aimed to evaluate the prognostic potential of HOXA5 in EC and to explore its association with common tumor-related proteins. Methods: We analyzed 75 EC tissue samples using immunohistochemistry to evaluate HOXA5 expression and its association with clinicopathological features and tumor-related biomarkers, including Ki-67, CD31, and fibronectin. Statistical analyses included logistic regression and Kaplan–Meier survival analysis. Results: High HOXA5 expression was significantly associated with elevated Ki-67 levels (p = 0.001) but paradoxically correlated with improved overall survival (p = 0.026). CD31 and fibronectin levels were significantly lower in the high-HOXA5 group (p = 0.007 and p = 0.001, respectively), suggesting reduced angiogenic and invasive potential. However, neither marker remained significant in multivariable analysis. Conclusions: HOXA5 may exert a dual role in EC by promoting proliferation while limiting tumor progression via suppression of angiogenesis and matrix remodeling. It holds potential as a prognostic biomarker and therapeutic target. Full article

Background: Despite advances in treatment, oral squamous cell carcinoma (OSCC) remains associated with high recurrence and mortality rates. Traditional TNM staging, while foundational, may not fully capture tumor aggressiveness. This study aimed to identify clinical and histopathological predictors of survival to enhance risk stratification and guide treatment planning in OSCC patients. Methods: A retrospective study of 100 patients with confirmed OSCC treated surgically with curative intent between January 2019 and January 2024 was analyzed. Clinicopathologic variables—including tumor volume, angioinvasion, perineural invasion, lymphatic invasion, and nodal status—were evaluated. Disease-specific survival (DSS) was assessed using Kaplan–Meier estimates, Cox regression, and logistic regression models. Results: The cohort had a mean age of 62.1 years, with a 46% OS rate and 43% DSS at study end. Perineural invasion (44%) and lymphatic invasion (42%) were the most common invasive features. Kaplan–Meier analysis revealed significantly reduced DSS in patients with angioinvasion, perineural invasion, and pN+ status. Multivariate logistic regression identified perineural invasion (OR = 3.93, p = 0.0023) and pN+ status (OR = 2.74, p = 0.0284) as independent predictors of cancer-specific mortality. Tumor volume was significantly associated with lymphatic invasion but not directly with DSS. Conclusions: Perineural invasion, angioinvasion, lymph node involvement, and tumor volume are important prognostic markers in OSCC, offering critical information beyond TNM staging. Incorporating these features into risk assessment models could improve prognostic accuracy and inform more individualized treatment strategies for high-risk OSCC patients. Full article

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

Lung adenocarcinoma exhibits a heterogeneous molecular landscape shaped by key oncogenic drivers and tumor suppressor gene alterations. Mutation frequencies vary geographically, influenced by genetic ancestry and environmental factors. However, the molecular profile of lung adenocarcinoma in Bulgarian patients remains largely uncharacterized. We conducted a prospective study of 147 Bulgarian patients with metastatic lung adenocarcinoma, analyzing clinicopathologic features and somatic mutation frequencies using next-generation sequencing. Key mutations and their prevalence were assessed and compared with published data from other populations. The cohort included predominantly male patients (68.0%) with a median age of 67 years. TP53 mutations were most frequent (41.5%), followed by EGFR alterations (19.0%) and KRAS c.34G>T (p.Gly12Cys) (17.0%). Over half of the patients (51.0%) harbored two or more gene mutations. Mutation frequencies aligned closely with European cohorts, exhibiting a lower prevalence of EGFR mutations compared to East Asian populations. This study characterizes the molecular landscape of lung adenocarcinoma in Bulgaria, highlighting the predominance of TP53 and KRAS mutations. The findings emphasize the need for comprehensive molecular profiling to inform targeted therapies and support precision oncology approaches tailored to the Bulgarian population. Further research is needed to validate these results and improve clinical outcomes. Full article

Individuals with immunosuppressive conditions are at a higher risk of developing malignancies than those in the general population. Immunosuppression weakens tumor immunity, hinders the detection of pro-oncogenic cells, and activates oncogenic viruses. Malignancies arising in immunosuppressed patients tend to be aggressive, have a high incidence of virus-associated cancers, and are reversible in some cases. Notably, immunosuppressive agents influence the frequency and type of malignancies, as well as their clinicopathological features. Organ transplant recipients receive long-term immunosuppressants to prevent acute rejection. Post-transplant malignancies vary depending on the type of drug administered before the onset of these diseases. Patients with rheumatoid arthritis (RA) are treated with long-term immunosuppressive medications, such as methotrexate (MTX). MTX is widely recognized as being associated with a specific type of lymphoproliferative disorder (LPD), known as MTX-associated LPD. Our recent report indicated that the clinicopathological features of rheumatoid arthritis-associated lymphoproliferative disorder (RA-LPD) also vary based on the other anti-RA agents used, such as tacrolimus and tumor necrosis factor inhibitors. Therefore, the clinicopathological characteristics of post-transplant LPD and RA-LPD evolve alongside the changes in the immunosuppressants/immunomodulators administered. Understanding the various characteristics and time trends of immunosuppressive neoplasms, particularly LPDs, in relation to different immunosuppressant/immunomodulator medications is highly valuable in clinical practice. Full article