BACKGROUND:Epstein-Barr virus (EBV)-positive small cell neuroendocrine carcinoma of the nasopharynx (SCNEC-nasopharynx) is exceptionally rare and aggressive, with poorly characterized molecular features. METHODS:Clinicopathological, immunohistochemical (synaptophysin, INSM1, chromogranin A, CK-pan, EGFR, NUT, INI1), and molecular profiles of 15 EBV-positive SCNEC-nasopharynx cases (2012-2025) were analysed. EBV status was confirmed by EBER-ISH. Exploratory next-generation sequencing compared nine SCNEC with five EBV-positive nasopharyngeal non-keratinizing carcinomas (NKUC). RESULTS:Patients (median age 51; male:female = 2:1) presented with advanced-stage disease and cervical lymphadenopathy. Histology showed solid nests of small cells with high-grade features. All tumours were diffusely positive for synaptophysin and EBER, showed perinuclear dot-like CK-pan staining, and were negative for squamous markers and EGFR. NUT was negative and INI1 retained. Comparative genomics revealed greater mutational burden and unique alterations enriched in cell cycle/DNA damage pathways in SCNEC versus NKUC. After multimodal therapy, median overall survival was 33 months. CONCLUSION:This largest integrated study defines the distinct clinicopathological and molecular profile of EBV-positive SCNEC-nasopharynx. The identified diagnostic immunophenotype and potential oncogenic pathways provide a foundation for precise diagnosis and future targeted therapy development.

This study aimed to assess the potential diagnostic utility of immune receptor translocation-associated protein 1 (IRTA1) and myeloid nuclear differentiation antigen (MNDA) expression in marginal zone lymphoma (MZL). We evaluated whole-tissue sections from 686 specimens; specifically, reactive lymphoid hyperplasia (n=60), MZL (n=284), follicular lymphoma (n=156), mantle cell lymphoma (n=64), chronic lymphocytic leukaemia/small lymphocytic lymphoma (n=51), lymphoplasmacytic lymphoma (n=17), and diffuse large B-cell lymphoma (DLBCL; n=54). Immunohistochemical staining for IRTA1, MNDA, and other markers (CD10, BCL-6, CD5, CD23, cyclin D1, SOX-11, and LEF-1) was performed using an automated system. IRTA1 was expressed in 62.3% (177/284) of MZL vs 8.7% (25/288) of other small B-cell lymphoma and 14.81% (8/54) of DLBCL specimens (p<0.001 and p<0.001, respectively). MNDA was expressed in 60.9% (173/284) of MZL vs 24.7% (71/288) of other small B-cell lymphoma and 25.93% (14/54) DLBCL specimens (p<0.001 and p<0.001, respectively). Expression of IRTA1 had a higher specificity than MNDA for MZL. Expression of either IRTA1+ or MNDA+ was detected in 78.9% (224/284) of MZL specimens, whereas coexpression was less common (44.4%, 126/284). Within MZL subtypes, IRTA1 and MNDA were expressed at lower frequencies in nodal MZL (55.7% and 55.7%, respectively) than in mucosa-associated lymphoid tissue lymphoma (64.1% and 62.7%, respectively). Expression of IRTA1 alone, or either IRTA1+ or MNDA+, was less frequent among MZL with plasma cell differentiation than among MZL with classical cell morphology (p=0.063 and 0.071, respectively), albeit not significantly. IRTA1 and MNDA are sensitive and specific markers for the differential diagnosis of MZL, and they may be helpful in distinguishing MZL from histologic mimics.

This study examined the prognostic significance of tumor budding (TB) and poorly differentiated clusters (PDCs) in 232 patients with primary cutaneous melanoma (CM). Through retrospective analysis and Cox regression models, TB-3 and ulceration were identified as independent prognostic factors for overall survival, while AJCC stage IV and PDCs were associated with progression-free survival. Additionally, factors such as ulceration, vascular invasion, lymph node metastasis, TB-3, PDCs, non-brisk tumor-infiltrating lymphocytes (TILs), and Breslow thickness were significantly linked to prognosis. A nomogram developed from these findings demonstrated strong predictive accuracy (AUC = 0.839). The results suggest that incorporating TB and PDCs into the current CM staging systems could enhance risk stratification and clinical decision-making.

The treatment principle for locally advanced cervical cancer is concurrent chemoradiotherapy (CCRT). However, local recurrence or distant metastasis may still occur after the completion of CCRT. Currently, there is no effective method to monitor the efficacy of CCRT and predict prognosis. This study aims to predict the therapeutic efficacy and prognosis by dynamically monitoring human papillomavirus (HPV) circulating tumor DNA (HPV ctDNA) levels. We enrolled 31 patients with locally advanced cervical cancer and used the HPV-Seq (14 subtypes) to quantify HPV genotype-specific DNA in plasma and tissues before and during CCRT, and in the post-treatment plasma. Regular imaging was performed to evaluate tumor regression. HPV reads in plasma and tissues decreased significantly during treatment (p < 0.05). Higher HPV ctDNA levels were associated with poorer treatment outcomes (p < 0.05). In univariate and multivariate analyzes, dynamic changes in plasma HPV ctDNA were an independent factor for predicting early treatment outcome. These findings indicate that longitudinal HPV ctDNA monitoring reflects the efficacy of CCRT in locally advanced cervical cancer and provides a basis for earlier identification of candidates for post-CCRT treatment intensive and prognostic stratification.

This study aimed to develop and validate a comprehensive model that uses clinicopathological and computed tomography (CT) imaging features to non-invasively predict epidermal growth factor receptor (EGFR) mutation subtypes in patients with lung adenocarcinoma (LUAD), offering a valuable reference for precise diagnosis and treatment. A total of 318 surgically resected LUAD cases were analyzed. EGFR gene mutations were identified using multiplex fluorescence polymerase chain reaction. Multivariate logistic regression analysis identified independent predictors for the L858R mutation (sex, follicle-predominant type, burr sign, and ground-glass nodule [GGN]); the 19-del mutation (sex, acinar dominant type, burr sign, and GGN); and rare mutations (solid dominant type, spread through air spaces [STAS], and burr sign). Based on these predictors, subtype-specific prediction models were constructed and visualized as nomograms. Predictive performance was assessed through internal validation, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis. The area under the curve (AUC) values for the L858R, 19-del, and rare mutation prediction models were 0.745, 0.863, and 0.792, respectively. Internal validation demonstrated favorable discrimination, calibration, and clinical utility. The EGFR mutation prediction model for LUAD developed in this study exhibited robust performance and may serve as a valuable tool for precise diagnosis and treatment planning in LUAD.

BACKGROUND:Achieving early and sensitive detection of esophageal cancer-related biomarkers in community healthcare settings is of great significance for the early screening, diagnosis, and intervention of diseases. RESULTS:This work developed a paper-based photoelectrochemical (PEC) immunosensing array loaded with thermally annealed ZnO nanocatalysts for the sensitive detection of ferritin, a biomarker of ferroptosis associated with the esophageal cancer, in community healthcare settings. A paper-based three-electrode system was mass-produced using screen printing technology, and thermally annealed ZnO nanocatalysts with excellent resistance to photo-corrosion were obtained and loaded onto the working electrode surface. The opposite region of the electrode was modified with ferritin-specific antibodies to enable target-specific capture and signal conversion. A one-step folding strategy was employed to directionally transfer the catalytic product, ascorbic acid, to the electrode interface, where it efficiently converts the biological signal into a photoelectric signal under excitation from a handheld flashlight. This sensor array demonstrated a wide linear detection range (0.1 - 50 ng mL-1) and a low detection limit (0.038 ng mL-1), while offering the advantages of low cost (1.0 $ per test), portability, and mass producibility. SIGNIFICANCE:This work provides a rapid and reliable diagnostic tool for the early screening of esophageal cancer-related diseases in community settings.

AIMS:Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell sarcoma (EBV+ IFDCS) is a rare, indolent malignant neoplasm. Due to its rarity, a comprehensive assessment of its immunophenotypic spectrum and molecular analysis is still lacking. This study aimed to characterize the immunophenotypic and genetic alterations of EBV+ IFDCS to improve understanding of its cell of origin and molecular pathogenesis and to identify potential therapeutic targets. METHODS AND RESULTS:Immunohistochemical staining for a panel of follicular dendritic cell (FDC) and fibroblastic reticular cell (FRC) lineage markers, along with targeted next-generation sequencing, was performed. Nineteen cases of EBV+ IFDCS were classified into four immunophenotypes: nine FDC, two FRC, three biphasic and five null phenotypes. Morphologically, cases with a null phenotype more frequently exhibited a lymphoma-like growth pattern (4/5, 80%) compared with those with a definite FDC and/or FRC phenotype (1/14, 7.1%, P = 0.006). Moreover, a scattered distribution of neoplastic cells was more commonly observed in null phenotype cases (4/5, 80%) than in FDC and/or FRC phenotype cases (3/14, 21.4%, P = 0.038). Targeted sequencing revealed somatic variants in chromatin modifier-related genes in 60.0% (9/15), homologous recombination repair (HRR)-related genes in 53.3% (8/15) and Hippo pathway-related genes (FAT2 and FAT1) in 26.7% (4/15) of cases. CONCLUSIONS:These findings demonstrate the wide morphological and immunophenotypic spectrum of EBV+ IFDCS. Furthermore, variants in chromatin modifier and HRR-related genes may participate in its pathogenesis, and PARP inhibition may represent a potential therapeutic strategy for patients with unresectable disease.

Background The differences in the clinical features, prognosis and genetic mutations in Chinese patients with malignant melanoma (MM) and additional primary tumours remain unclear.Methods A retrospective analysis was conducted on patients with malignancies in Fujian Cancer Hospital from January 2007 to September 2022, end follow-up in September 2023. Clinical data were gathered, survival analysis was performed, and genetic mutations were detected.Results There were 58 of 1223 melanoma patients with melanoma and additional primary tumours, an incidence of 4.74%. Acral MM was the most common subtype (26/58), 23 (39.66%) patients had concomitant digestive tumours. Patients who had MM as their first primary tumour (MMFP) had shorter tumour occurrence intervals (9.93 vs. 57.78 months, p = .008) but longer melanoma survival (MM-OS) than the non-MMFP group (100.43 vs. 18.93 months, p = .015). Patients with cancer family histories were more likely to have pathogenic and likely pathogenic (P/LP) mutations (2/5 vs. 4/25). The somatic BRAF gene mutation was frequently observed in MM tissue (8/19, 42.11%). Three patients had whole-genome doubling and microsatellite instability-high (MSI-H). The COSMIC2 signature 3 was significantly higher in the P/LP group.Conclusions The frequency of MM and additional primary tumours is about 5% in Chinese populations. Patients with melanoma diagnosed first have longer melanoma survival. Digestive system tumours were the most concomitant; a digestive examination is advisable, especially for those with an expected overall survival (OS) greater than 10 months. Meanwhile, patient’s family cancer history should be followed up in detail, along with completion of germline P/LP mutation and somatic mutation testing, all of which may provide valuable support for further treatment.

The BRAFV600E mutation test for melanoma patients has become the key to precision therapy. In this study, we compared the concordance of immunohistochemistry (IHC), quantitative real-time PCR (qPCR), and next-generation sequencing (NGS) in detecting the BRAFV600E mutation in a Chinese melanoma patient population. In addition, this study evaluated the BRAFV600E mutation heterogeneity between primary and metastatic melanoma sites, as well as within the same lesion, and investigated the association between BRAFV600E mutation status and tumor cell morphology. A total of 880 samples from 555 patients diagnosed with malignant melanoma were collected, and IHC for BRAFV600E was conducted. Of these, 385 were subjected to qPCR and 115 to NGS concurrently. Inter and intratumor heterogeneities of BRAFV600E mutations were compared. Hematoxylin and eosin (H&E) stain was performed, and the cell morphologies were reviewed. The IHC and qPCR results were discordant in 14 cases, yielding a concordance rate of 96.36%. IHC and NGS results showed a concordance rate of 97.39%. The sensitivity and specificity of BRAFV600E detection by IHC were 96.95% and 99.46%, with an overall concordance rate of 98.80%. One of 130 patients (0.77%) showed intertumor heterogeneity, and 3 of 880 samples (0.34%) showed intratumor heterogeneity. VE1 staining patterns significantly differed across cell morphologies (P < .01). Compared with qPCR and NGS, VE1 IHC offers high sensitivity, specificity, and consistency in detecting the BRAFV600E mutation in melanomas. The BRAFV600E mutation in melanoma exhibits low intertumor and intratumor heterogeneities and is significantly associated with tumor cell morphology; tumors with epithelioid cell morphology are most likely to harbor the BRAFV600E mutation.

A new nanoparticles-based sensing platform was designed for high-through electrochemical immunoassay of ferritin (FET) biomarker on a magneto-controlled microfluidic device by using anti-FET capture antibody-conjugated magnetic sensing probes. Thionine-doped calcium carbonate (CaCO3) nanoparticles labeled with anti-FET detection antibodies were utilized as the recognition elements. Introduction of target FET caused the sandwich-type immunoreaction between two antibodies. The formed immunocomplexes were attached onto magnetic microfluidic sensing interface through an external magnet. Subsequently, the carried CaCO3 nanoparticles were dissolved under acidic conditions to release the doped thionine molecules with redox activity. The thionine-based voltammetric signals increased with the increment of target FET levels within the linear range 0.01–100 ng mL−1. The limit of detection was 7.9 pg mL−1 FET. Good analytical properties such as selectivity, reproducibility, and accuracy were achieved with the nanoparticles-based magnetic electrochemical immunoassay. More significantly, the magnetic microfluidic electrochemical immunoassay provides new opportunities for rapid, simple, and cost-effective serum sample analysis.

DNA methylation is a promising biomarker for early cancer detection; however, traditional detection methods require bisulfite treatment and nucleic acid amplification, which are costly and impractical for point-of-care use. We propose a facile method that leverages immunoassays and surface-enhanced Raman scattering (SERS) readouts for the multiplex, sensitive, and portable detection of lung cancer-related DNA methylation biomarkers. This approach employs 5-methylcytosine antibody-modified magnetic probes to enrich methylated DNA sequences and uses core-shell nanoparticles with Probe DNA as SERS nanotags for multiplex detection, eliminating the need for bisulfite treatment and nucleic acid amplification. The multiplex SERS immunoassay detects synthetic methylated SHOX2 and RASSF1A with detection limits of 0.52 pM and 0.66 pM, respectively. It shows a strong correlation with quantitative PCR results in analyzing methylated SHOX2 and RASSF1A from cell lines and formalin-fixed paraffin-embedded tissue samples (n = 35). Additionally, the random forest analysis based on methylated SHOX2 and RASSF1A expression distinguishes lung cancer from benign lung diseases with a clinical sensitivity of 96 %, specificity of 90 %, and an AUC value of 0.972. This method offers a significant advancement for DNA methylation research and clinical applications.

OBJECTIVE:Uterine cancer (UC) is a major cause of cancer-related deaths among women. This study assesses the global burden of UC from 1990 to 2021. METHODS:Data from the Global Burden of Disease 2021 study were used to analyze UC incidence, mortality, and disability-adjusted life years (DALYs) across 204 countries. Age-standardized rates were evaluated by age and Socio-Demographic Index (SDI), with trends forecasted to 2036 using Bayesian models. RESULTS:In 2021, the global incidence of UC reached 473,614 cases (95% uncertainty interval [UI]=4,29916-5,13667), with an age-standardized incidence rate of 5.41 per 100,000 (95% UI=4.90-5.87), showing an upward trend since 1990, particularly in high-SDI regions. However, the mortality rate in high SDI regions exhibited a declining trend, with an estimated annual percentage change (EAPC) of -0.25 (95% confidence interval=-0.42 to -0.08). Although the number of deaths globally has increased, the age-standardized mortality rate has decreased compared to 1990 (EAPC: -0.85). The global age-standardized DALYs also show a downward trend, except in high SDI and low-middle SDI regions. The highest incidence was observed among individuals aged 70-74 in 2021. By 2036, new cases are projected to rise, though incidence, mortality, and DALYs are expected to decline. CONCLUSION:Regional disparities in the global UC burden highlight the need for tailored strategies, especially in low-income countries, to reduce its impact.

Cervical cancer (CC) is a significant cause of cancer-related deaths in women and ranks as the fourth most common malignant tumor worldwide. Cervical histopathology is currently the primary diagnostic method for confirming the presence of CC. Tumor markers and imaging techniques play crucial roles in monitoring treatment effectiveness and prognostic follow-up. Unfortunately, these traditional examination methods are invasive and often lack sensitivity and accuracy. Therefore, there is a need for a less invasive and more sensitive test to facilitate early diagnosis, efficacy evaluation, and prognostic monitoring of CC. In recent years, liquid biopsy has been developed as a new detection method. It involves analyzing tumor components released into the peripheral circulation, such as cell-free RNA, circulating tumor DNA, circulating tumor cells, tumor-educated platelets, and exosomes. Liquid biopsy offers advantages such as being less invasive, highly reproducible, and capable of real-time monitoring. Moreover, liquid biopsy can play a crucial role in the early diagnosis of CC, guiding targeted therapy, assessing prognosis, and evaluating treatment effectiveness. This review focuses on the value of liquid biopsy application in CC, detection markers, and detection methods. It also explores how liquid biopsy can be used in the detection, prognosis, and monitoring the progression of CC. The advantages and limitations of liquid biopsy in CC are analyzed to promote its application and improve the diagnosis and treatment of the disease.

The presence of a micropapillary (MPP) component is a crucial determinant of surgical strategies for lung adenocarcinoma (LUAD), yet reliable blood biomarkers for predicting MPP⁺ LUAD remain elusive. Here, we integrate 4D label-free quantitative proteomics, a nanomixing-enhanced microfluidic surface-enhanced Raman spectroscopy (SERS) platform, and machine learning to sensitively identify and validate blood protein biomarkers associated with MPP⁺ LUAD. Comparative proteomics reveal 44 differentially expressed proteins (DEPs) between MPP⁺ and MPP⁻ LUADs, with bioinformatics uncovering their roles in MPP⁺ LUAD formation. To enable sensitive, multiplex detection of 4 upregulated DEPs, the nanomixing effect is leveraged to enhance target protein-SERS barcode interactions while minimizing nonspecific binding to antibody-functionalized gold electrodes. The SERS barcode cocktail allows simultaneous detection of the 4 selected DEPs. Machine learning models based on SERS detection effectively distinguish MPP⁺ from MPP⁻ LUAD patients, as well as LUAD patients from healthy donors. This approach demonstrates strong diagnostic potential for early, non-invasive MPP detection in LUAD, advancing nanotechnology-driven disease diagnosis and monitoring.