Pathology, research and practice最新文献

{"title":"From inflammation to carcinogenesis: Distinct pathways and clinical implications of IBD-associated colorectal cancer compared with sporadic CRC","authors":"Anshu Kapadia ,&nbsp;Drasti Joshi,&nbsp;Ankit Chavda,&nbsp;Parloop Bhatt","doi":"10.1016/j.prp.2025.156249","DOIUrl":"10.1016/j.prp.2025.156249","url":null,"abstract":"<div><div>Inflammatory bowel disease-associated colorectal cancer (IBD-CRC) represents a distinct clinical and molecular entity compared with sporadic colorectal cancer (CRC). While sporadic CRC arises through the adenoma–carcinoma sequence, IBD-CRC follows an inflammation–dysplasia–carcinoma pathway, characterized by early TP53 alterations, multifocality, and flat lesions that challenge detection. Contemporary epidemiology indicates declining IBD-CRC incidence in high-income regions due to improved surveillance, though risk remains elevated in subgroups with long-standing colitis, primary sclerosing cholangitis (PSC), or persistent inflammation. In contrast, underreporting in low- and middle-income countries obscures the true global burden. Advances in high-definition colonoscopy and chromoendoscopy have improved detection, yet optimal risk-adapted surveillance strategies remain underutilized. Molecular insights highlight differences in genetic alterations, immune evasion, and microbial drivers between IBD-CRC and sporadic CRC. This review synthesizes epidemiologic, pathogenetic, and clinical distinctions, underscores challenges in surveillance and reporting, and discusses emerging technologies—including liquid biopsy, artificial intelligence, and multi-omics—that may refine prevention and early detection. Recognition of IBD-CRC as a separate disease process is essential to optimize individualized risk stratification, surveillance algorithms, and therapeutic strategies.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156249"},"PeriodicalIF":3.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LINC00673 promotes osteosarcoma progression through the miR-92b-3p/DUSP1 axis","authors":"Kailiang Zhang ,&nbsp;Mingrui Du ,&nbsp;Ming Chen ,&nbsp;Yinglong Zhang ,&nbsp;Kuohao Shi ,&nbsp;Dawei Zhang ,&nbsp;Xin Wang ,&nbsp;Yong Zhou","doi":"10.1016/j.prp.2025.156253","DOIUrl":"10.1016/j.prp.2025.156253","url":null,"abstract":"<div><h3>Background</h3><div>An increase body of research indicates that long non-coding RNAs (lncRNAs) play a critical role in the development of osteosarcoma. This study investigates the function and molecular mechanism of LINC00673 in the progression of osteosarcoma.</div></div><div><h3>Methods</h3><div>Quantitative reverse transcription-PCR (qRT-PCR) was employed to assess the expression levels of LINC00673 in osteosarcoma cells and tissues. Additionally, we evaluated the correlation between LINC00673 expression in osteosarcoma tissues and the clinicopathological characteristics of patients. Various assays, including CCK-8, Colony formation assay, Transwell assay, and nude animal model experiments, were conducted to investigate the biological function of LINC00673 in osteosarcoma both in vivo and vitro. Downstream target genes of LINC00673 were identified through whole transcriptome sequencing and bioinformatics tools, followed by validation using qRT-PCR, western blotting, RNA immunoprecipitation (RIP) assay, dual-luciferase reporter gene assay and rescue experiments.</div></div><div><h3>Results</h3><div>In our study, we found that LINC00673 is highly expressed in osteosarcoma cells and tissues. The upregulation of LINC00673 was positively correlated with advanced clinical stages and distant metastasis in patients with osteosarcoma. The knockdown of LINC00673 suppressed both cell proliferation and metastasis of osteosarcoma in vivo and vitro. Subsequent mechanistic studies revealed that LINC00673 functions as a competing endogenous RNA (ceRNA). enhancing DUSP1 expression by sponging miR-92b-3p.</div></div><div><h3>Conclusions</h3><div>LINC00673 functions as an oncogenic lncRNA in osteosarcoma by enhancing the malignant phenotype of osteosarcoma through miR-92b-3p/DUSP1 axis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156253"},"PeriodicalIF":3.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disrupted rhythms and dysfunction: A chronobiological perspective on polycystic ovary syndrome","authors":"Ishanka Singh,&nbsp;Pawan Kumar Maurya","doi":"10.1016/j.prp.2025.156251","DOIUrl":"10.1016/j.prp.2025.156251","url":null,"abstract":"<div><div>Polycystic Ovary Syndrome (PCOS) is a multifactorial endocrine-metabolic disorder characterized by reproductive irregularities, hyperandrogenism, and insulin resistance. Recent advances in chronobiology have introduced a compelling narrative suggesting that dysregulation in circadian system is a contributing factor in the pathogenesis and clinical manifestation of PCOS. This review explores how disrupted biological timing—reflected in misaligned central and peripheral clocks, altered melatonin dynamics, and irregular sleep-wake cycles—intersects with metabolic and hormonal dysfunctions in PCOS. We highlight emerging evidence linking aberrant expression of clock genes such as CLOCK, BMAL1, and PER1 in ovarian, hepatic, and hypothalamic tissues to ovulatory failure, insulin resistance, and androgen excess. Moreover, melatonin, a key circadian hormone, demonstrates altered systemic and follicular profiles in PCOS, influencing folliculogenesis, oxidative stress, and steroidogenesis. Further, this review delves into the neuroendocrine pathways by which circadian cues modulate the hypothalamic-pituitary-ovarian axis and how their disruption may contribute to reproductive impairment. In light of these findings, we discuss chronotherapeutic approaches—including melatonin supplementation, time-restricted feeding, light therapy, and circadian-timed pharmacotherapy—as emerging strategies for personalized and temporally aligned PCOS treatment. Despite limitations in clinical standardization and the need for biomarker-based stratification, chronomedicine offers a promising adjunct to traditional PCOS management. By framing PCOS as a disorder of temporal dysregulation, this review advocates for a paradigm shift in both understanding and treating the syndrome, paving the way toward circadian-informed clinical care.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156251"},"PeriodicalIF":3.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of peritoneal fluid for multiplexed mRNA profiling of peritoneal metastasis from pancreatic cancer","authors":"Sharuya Kulatheivam ,&nbsp;Lea Lecanda Mariager Jakobsen ,&nbsp;Mark Burton ,&nbsp;Alan P. Ainsworth ,&nbsp;Claus Fristrup ,&nbsp;Martin Graversen ,&nbsp;Michael B. Mortensen ,&nbsp;Per Pfeiffer ,&nbsp;Line S. Tarpgaard ,&nbsp;Sönke Detlefsen","doi":"10.1016/j.prp.2025.156250","DOIUrl":"10.1016/j.prp.2025.156250","url":null,"abstract":"<div><h3>Background</h3><div>Patients with peritoneal metastasis (PM) have poor survival rates, and few methods for prognostic stratification of patients with proven PM exist. Peritoneal fluid (PF) provides a direct reflection of the microenvironment of the peritoneal cavity, and transcriptomic profiling of PF represents a novel and potentially clinically valuable approach that warrants investigation. We aimed to evaluate the utility of formalin-fixed paraffin embedded (FFPE) PF sediments left over after conventional peritoneal cytology diagnosis for multiplexed mRNA expression profiling and to identify dysregulated mRNAs in PM vs. controls. Furthermore, we explored whether certain mRNAs upregulated in PM hold prognostic value.</div></div><div><h3>Methods</h3><div>Samples included were FFPE sediments of malignant PFs from cases of PM from pancreatic cancer (PM-PC, n = 19) scheduled for pressurized intraperitoneal aerosol chemotherapy (PIPAC) and benign ascites (controls, n = 16). RNA was extracted from the FFPE sediments. Expression profiling of 760 cancer-related mRNAs was performed, followed by unsupervised clustering, differential gene expression analysis, ROC/AUC analysis, generation of KM plots, and Cox proportional hazards regression. Cellular expression of proteins encoded by selected dysregulated mRNAs was analyzed using immunocytochemistry.</div></div><div><h3>Results</h3><div>In PF sediments with malignant cells, 56 upregulated and 130 downregulated mRNAs were identified. Selected up- and downregulated mRNAs were similarly dysregulated at the protein level. Upregulation of six mRNAs (ESRP2, EPCAM, SFN, ITGB6, ESRP1, and GRHL2) was associated with short-term survival (P &lt; 0.0025).</div></div><div><h3>Conclusion</h3><div>Our data indicate that PF from PM-PC patients is suitable for transcriptomic analysis. Numerous upregulated mRNAs known to play a role in tumour progression were identified. Our data indicate that mRNA profiling may be a clinically useful tool for further prognostic stratification of patients with proven PM, but larger studies are needed to validate our findings.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156250"},"PeriodicalIF":3.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An interpretable machine learning framework for automated mitosis detection in gastrointestinal stromal tumors","authors":"Xin Dong,&nbsp;Jiaqiang Dong,&nbsp;Kai Liu,&nbsp;Min Niu,&nbsp;Yue Wang,&nbsp;Liwen Miao,&nbsp;Yitong Zhe,&nbsp;Ying Han,&nbsp;Zhiguo Liu","doi":"10.1016/j.prp.2025.156246","DOIUrl":"10.1016/j.prp.2025.156246","url":null,"abstract":"<div><div>The mitotic index is a critical indicator in grading gastrointestinal stromal tumors (GIST). Conventional microscopy-based mitosis counting is labor-intensive and exhibits interobserver variability, necessitating automation. However, existing models have proven unsuitable for GIST spindle cells. To address this limitation, we developed a machine learning method for automated mitosis detection in GIST. A GIST image database, annotated with 13,965 mitotic cells, was first established. Following nuclei segmentation, feature extraction, and feature selection, six different algorithms were employed to train mitosis detection models on images at both 10 × and 40 × magnification levels. The Radial Basis Function Support Vector Machine (SVM-RBF) achieved the best performance under both magnifications (10 ×: F1 = 0.83; 40 ×: F1 = 0.89). Slide-level mitosis counting was then performed via a two-step cascaded dual-scale approach, in which the 10 × model first identified Regions of Interest (ROIs), followed by precise detection and counting using the 40 × model. Slide-level validation showed a moderate correlation between automated and manual mitosis counts (r = 0.4705) and a strong correlation between the automated counts and Ki-67 expression (r = 0.6187). SHAP interpretability analysis confirmed that the model's decision-making basis closely aligned with pathologists' diagnostic criteria, including nuclear membrane disintegration, chromatin condensation, and chromosomal alignment. In summary, this study establishes the first automated framework for mitotic cell detection and counting in GIST. It underscores the clinical potential of traditional machine learning for targeted pathological applications and demonstrates favorable interpretability.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156246"},"PeriodicalIF":3.2,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Expression of pro-fibrotic and anti-fibrotic molecules in dimethylnitrosamine-induced hepatic fibrosis” Pathol. – Res. Pract. 213 (2017) 58–65","authors":"Roberta Sferra ,&nbsp;Antonella Vetuschi ,&nbsp;Simona Pompili ,&nbsp;Eugenio Gaudio ,&nbsp;Silvia Speca ,&nbsp;Giovanni Latella","doi":"10.1016/j.prp.2025.156239","DOIUrl":"10.1016/j.prp.2025.156239","url":null,"abstract":"","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156239"},"PeriodicalIF":3.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling PCOS therapies: Pharmacotherapeutic strategies and emerging therapeutic targets","authors":"Kamini R. Shirasath ,&nbsp;N. Zaheer Ahmed ,&nbsp;Pawan Kumar ,&nbsp;Shah Alam ,&nbsp;Ritu Karwasra ,&nbsp;Sameer N. Goyal ,&nbsp;Yogeeta O. Agrawal","doi":"10.1016/j.prp.2025.156245","DOIUrl":"10.1016/j.prp.2025.156245","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS) is a common health problem that can affect the reproductive health of women. A typical characteristic of PCOS is infertility, androgen excess, and anovulation. In addition, a disorder also accompanies other pathologies like obesity and hyperinsulinemia, with an increased threat of cardiovascular complications. Current treatment strategies focus on the reduction of PCOS symptoms primarily through pharmacological medications such as metformin, oral contraceptives, and anti-androgenic agents. Since these medications do not encompass all the outcomes of PCOS, there is a critical need for research to identify more effective treatments. Given the rising global prevalence of PCOS and its association with cardiovascular and metabolic risks, there is an urgent need for better therapeutic options with minimal adverse effects. This review integrates the current pharmacotherapies and emerging molecular and cellular targets, offering novel directions for comprehensive PCOS management. Additionally, this review explores various novel targets such as neuropeptides, inflammasome, anti-inflammatory agents, gene therapy/microRNA (miRNA) based therapies, adipokines-based therapies and stem cells-based therapy. Furthermore, we highlight key areas requiring further research to improve PCOS management.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156245"},"PeriodicalIF":3.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic-epigenetic rewiring in cancer: The role of lactylation in tumor progression, immune evasion, and therapy resistance","authors":"Mokhtar Rejili","doi":"10.1016/j.prp.2025.156244","DOIUrl":"10.1016/j.prp.2025.156244","url":null,"abstract":"<div><div>Research shows that lysine lactylation (kla) represents a novel post-translational modification that links cancer metabolism with epigenetic regulation. The production of lactate through the Warburg effect is associated with the lactylation of both histone and non-histone proteins, which regulate key gene expression programs linked to tumor progression, therapy resistance, and immune evasion. This review integrates recent findings on how elevated glycolysis levels, along with increased lactate concentrations in the tumor microenvironment (TME), trigger transcriptional activation through lactylation-mediated mechanisms. It highlights how lactylation interacts with other acylations, contributes to the development of cancer stemness, remodels the immune landscape, and reduces drug efficacy across various tumor types. Elevated lactylation expression correlates with poor patient outcomes, diminished CD8⁺ T cell infiltration, and increased expression of immune checkpoint proteins at tumor sites, thereby creating an immunosuppressive environment. The survival of cancer cells depends in part on lactylation, as it enhances DNA repair efficiency, protects against ferroptosis, and regulates genes associated with therapeutic resistance. Researchers are currently evaluating novel therapeutics that target enzymes involved in lactate metabolism (LDH, MCTs) and epigenetic \"writers\" of lactylation, such as p300/ CREB-binding protein, to disrupt oncogenic signaling pathways. The diagnostic relevance of lactylation is also gaining attention, as it serves as a potential biomarker for tumor progression and treatment response. As a critical epigenetic regulatory mechanism, lactylation opens new avenues for the development of precise cancer therapies, warranting further in-depth investigation.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156244"},"PeriodicalIF":3.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative computational and experimental validation of Piperlongumine as a therapeutic agent targeting differentially expressed genes in colorectal cancer","authors":"Rajeev Kumar Sahoo ,&nbsp;Zahid Alim Ansari ,&nbsp;Sambit Kumar Pradhan,&nbsp;Bijesh Kumar Biswal","doi":"10.1016/j.prp.2025.156243","DOIUrl":"10.1016/j.prp.2025.156243","url":null,"abstract":"<div><div>Colorectal cancer (CRC) remains a major global health concern due to its high incidence and mortality. Recent studies have shown the potential of phytocompounds in CRC therapeutics. This study explores the anticancer potential of Piperlongumine (PIP), a natural phytocompound, in CRC through an integrative bioinformatics and experimental approach. Initially, integrative computational databases of GEO, CTD and GeneCards resulted in 11 common differentially expressed genes potentially targeted by PIP in CRC, showing involvement in multiple signaling pathways and apoptotic signaling. Further, protein-protein interaction analysis identified five hub genes- TP53, CCND1, AKT1, CTNNB1 and IL1B, showing significant expression alterations and correlations with poor prognosis and metastasis in CRC. The molecular docking demonstrated strong binding affinity between PIP and hub genes, alongside favorable pharmacokinetics including high gastro-intestinal absorption and minimal toxicity. Experimental validations on CRC cell lines- SW-480 and HT-29 revealed dose-dependent cytotoxicity with IC₅₀ values of 3 μM and 4 μM, respectively. In addition, <em>in vitro</em> assays confirmed PIP’s cytotoxic, anti-migratory, pro-apoptotic effects, and modulation of hub genes (TP53↑; CCND1, AKT1, CTNNB1, IL1B↓), supporting its mechanistic role in CRC. Together, these findings support that PIP exerts anticancer effects through modulation of hub genes, thus making it a potential therapeutic agent against CRC. This study is relevant as it bridges computational predictions with experimental validation, providing a systematic framework for natural compound evaluation in CRC. Unlike previous reports, this study uniquely combines multi-dataset transcriptomics, hub-gene prioritization, and ADMET profiling with <em>in-vitro</em> gene-level validation, which has not been previously reported for PIP in CRC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156243"},"PeriodicalIF":3.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological features of SMARCA4-deficient non-small cell lung cancer","authors":"Lu Han ,&nbsp;Li Chen ,&nbsp;Leiming Wang","doi":"10.1016/j.prp.2025.156241","DOIUrl":"10.1016/j.prp.2025.156241","url":null,"abstract":"<div><h3>Background</h3><div>SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC) is a poorly differentiated tumor with dismal prognosis. Currently, there are few molecular features reported on this type of tumor, and exploring the clinico-pathological features of SMARCA4-dNSCLC is crucial for prognosis and investigating treatment options.</div></div><div><h3>Methods</h3><div>Immunohistochemistry (IHC) was used to detect the expression of CK, Vimentin, CK7, TTF-1, Napsin-A, P40, CK5/6, Syn, CD34, SALL-4, SOX2, BRG-1, INI-1, PD-L1, and Ki-67 in 9 patients. DNA-based Next-generation sequencing (NGS) technology for tumor-related mutations was applied to detect the relevant molecular characteristics in 6 patients.</div></div><div><h3>Results</h3><div>Among the 9 patients, 8 were male and 1 was female; 6 had a long-term smoking history (10–60 years, 3–40 cigarettes/day); 6 presented with lymph node or bone metastases. For IHC, CK7 was strong positive in all cases. CD34 was negative in all. BRG-1 was consistently absent. INI-1 was not lost in any case. Napsin-A and P40 were positive in 1/9 cases. Vimentin, TTF-1, and Syn were positive in 2/9 cases. CK5/6, SALL-4, and SOX-2 were partially positive in 3/9 cases. PD-L1 expression demonstrated heterogeneous distribution: 33.3 % (3/9) of cases showed negative expression, 55.6 % (5/9) exhibited low expression, and 11.1 % (1/9) demonstrated high expression. and the Ki-67 proliferation index ranged from 20 % to 90 %. Among the 6 patients who underwent genetic testing, <em>SMARCA4</em> gene mutations were detected in 4 cases (4/6), while <em>TP53</em> gene mutations were present in all 6 cases (6/6). Genetic alterations in <em>LRP1B</em> were observed in 4 patients (4/6), and <em>KEAP1</em> gene changes were identified in 3 cases (3/6). <em>STK11</em> gene alterations were found in 2 patients (2/6), whereas <em>EGFR</em> gene mutation was only detected in 1 case (1/6). None of the 6 patients showed genetic changes in <em>KRAS</em>, <em>ROS</em>, or <em>ALK</em> genes. Regarding tumor mutational burden (TMB), 3 cases demonstrated low TMB frequency while the other 3 exhibited high TMB.</div></div><div><h3>Conclusion</h3><div>This study analyzed the clinicopathological characteristics and immunohistochemical profiles of 9 cases of SMARCA4-dNSCLC, and performed next-generation sequencing on 6 of these cases to preliminarily investigate the molecular genetic alterations in this tumor type. The findings provide reference value for clinicopathological diagnosis and treatment strategy formulation. However, due to limitations including the small sample size and relatively short follow-up period, the conclusions of this study require validation through larger cohort studies. Future work will focus on expanding the sample size, extending follow-up duration, and initiating multicenter collaborations to further elucidate the clinicopathological and molecular characteristics of this disease.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156241"},"PeriodicalIF":3.2,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}