Pathology, research and practice最新文献

{"title":"BRCA1 and BRCA2 mutations testing in prostate cancer: Detection in formalin fixed paraffin embedded (FFPE) and blood samples","authors":"Giuseppa Zannini ,&nbsp;Gaetano Facchini ,&nbsp;Marco De Sio ,&nbsp;Ferdinando De Vita ,&nbsp;Francesca Pagliuca ,&nbsp;Renato Franco ,&nbsp;Federica Zito Marino","doi":"10.1016/j.prp.2024.155803","DOIUrl":"10.1016/j.prp.2024.155803","url":null,"abstract":"<div><div>Prostate cancer (PC) represents one of the leading causes of cancer-related morbidity and mortality in men, requiring further understanding to improve diagnosis and treatment. Germline <em>BRCA1/2</em> mutations, primarily identified in other hereditary cancers, confer an increased risk of developing PC; thus, testing is essential to assess cancer risk, guiding preventive strategies and screening. Recently, somatic <em>BRCA1/2</em> mutations have emerged as pivotal predictive biomarkers of responsiveness to the poly ADP-ribose polymerase (PARP) inhibitors. This review provides a comprehensive overview of <em>BRCA1/2</em> mutations testing in PC, focusing on the germline and somatic mutations frequencies and the technical approach for their identification. A revision of the main data reported in the literature regarding <em>BRCA1/2</em> mutations identification will be presented, highlighting the critical issue for the detection both in formalin fixed paraffin embedded (FFPE) and blood samples.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155803"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell of origin and expression profiles of pseudomyxoma peritonei derived from the appendix","authors":"Rei Noguchi ,&nbsp;Kiyoshi Yamaguchi ,&nbsp;Hideaki Yano ,&nbsp;Yoshimasa Gohda ,&nbsp;Tomomichi Kiyomatsu ,&nbsp;Yasunori Ota ,&nbsp;Toru Igari ,&nbsp;Norihiko Takahashi ,&nbsp;Tomoyuki Ohsugi ,&nbsp;Kiyoko Takane ,&nbsp;Tsuneo Ikenoue ,&nbsp;Atsushi Niida ,&nbsp;Eigo Shimizu ,&nbsp;Rui Yamaguchi ,&nbsp;Satoru Miyano ,&nbsp;Seiya Imoto ,&nbsp;Yoichi Furukawa","doi":"10.1016/j.prp.2024.155776","DOIUrl":"10.1016/j.prp.2024.155776","url":null,"abstract":"<div><div>Pseudomyxoma peritonei (PMP) is a rare disease caused by mucin-producing tumors that develop most frequently from the appendix. The disease is characterized by the accumulation of mucin in the abdominal cavity. Although frequent mutations in the <em>KRAS</em> and <em>GNAS</em> genes have been reported in PMP, gene expression profiles of the tumors remain to be fully clarified because of its rarity and the difficulties in collecting pure cancerous cells scattered within the mucin. To disclose the molecular features of PMP cells, we performed RNA-seq analysis of ten PMPs and their matched non-tumorous colonic epithelium in combination with laser-microdissection. As a result, we identified a total of 32 differently expressed genes (DEGs) between the tumors and non-tumorous colonic epithelium. A cell-of-origin subtype analysis with the nearest template prediction algorithm corroborated that PMP tumor cells belonged to the goblet cell subtype, and tumorous cells of PMP appear to arise from goblet cells. Interestingly, over representation analysis (ORA) uncovered that the tumors were significantly associated with three ontology terms, namely epithelial mesenchymal transition (EMT), angiogenesis, and inflammatory response. Comparison of gene expression profiles between disseminated peritoneal adenomucinosis (DPAM) and peritoneal mucinous adenocarcinomas (PMCA) identified a total of 687 DEGs. Additional gene set enrichment analysis (GSEA) revealed that ontology terms “G2M checkpoint” and “E2F targets” were significantly enriched in PMCA supporting the view that PMCA has more aggressive properties than DPAM. These data may be useful to further understand the molecular characteristics of PMP.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155776"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automate the process of formalin-fixed paraffin-embedded blocks storage in the pathology laboratory: A proof of concept study","authors":"Albino Eccher ,&nbsp;Stefano Marletta ,&nbsp;Fabio Pagni ,&nbsp;Vincenzo L’Imperio ,&nbsp;Federico Piacentini ,&nbsp;Massimo Dominici ,&nbsp;Alberto Cavazza ,&nbsp;Carmine Pinto ,&nbsp;Matteo Brunelli ,&nbsp;Michelangelo Fiorentino ,&nbsp;Umberto Malapelle ,&nbsp;Marco Maria Baron ,&nbsp;Guido Martignoni ,&nbsp;Angelo Paolo Dei Tos","doi":"10.1016/j.prp.2024.155802","DOIUrl":"10.1016/j.prp.2024.155802","url":null,"abstract":"<div><div>Pathology laboratories are currently facing remarkable issues in the management of their archives due to the ongoing increase in the production of formalin-fixed paraffin-embedded (FFPE) blocks, which is often coupled with inadequate spatial and environmental storing conditions. The manual process of storage and retrieving further increases the likelihood of human-based mistakes, wastes professionals’ working time, and, ultimately, widens reports signing turn-around times. In the present work, we outline the strategies underlying the development of an automated archive at the pathology services of the University of Modena. The proposed project relies on the controlled interaction of a mechanic robotic arm with racks and shelves in a fully traced manner, driven by the integration with the local laboratory information system (LIS). This automated archive aims to significantly improve the time-saving of laboratory professionals and standardize the storage of FFPE samples both before and after the pathology diagnosis is rendered. The system's modularity suits the needs and spaces of the different institutions, opening novel strategies in archiving thanks to its connection with the LIS and integration with artificial intelligence algorithms.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155802"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927713","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":"Intra-patient comparison of microarchitecture of tumour negative lymph nodes from oesophageal cancer patients – Results from the MRC Oe02 trial","authors":"Maximilian Kloft ,&nbsp;Elzbieta Budginaite ,&nbsp;Sander M.J. van Kuijk ,&nbsp;Gayatri Raghuram ,&nbsp;Derek R. Magee ,&nbsp;Matthew G. Nankivell ,&nbsp;David Cunningham ,&nbsp;William H. Allum ,&nbsp;Ruth E. Langley ,&nbsp;Heike I. Grabsch","doi":"10.1016/j.prp.2025.155818","DOIUrl":"10.1016/j.prp.2025.155818","url":null,"abstract":"<div><h3>Background</h3><div>Regional lymph node (LN) status is a key prognostic factor in oesophageal cancer (OeC). Tumour-derived antigens can activate immune reactions in LNs, potentially reflecting the host’s anti-tumour immune response. It remains unclear whether this response is homogeneous across all tumour negative LNs (LNneg) within individual OeC patients.</div></div><div><h3>Purpose</h3><div>To investigate the hypotheses: (1) the host anti-tumour immune response is similar in all LNneg from an individual OeC patient reflected in a similar microarchitecture in all LNneg; and (2) immune response measured in the largest LNneg can represent that of all LNnegs.</div></div><div><h3>Methods</h3><div>(y)pN0 patients from the Oe02 trial with at least two LNneg were included. Microarchitectural LN features (germinal centres (GermC), lymphocytes outside GermCs (lymphocytes), histiocytes) were morphometrically quantified. Linear mixed-effects models, intraclass correlation coefficients (ICC) and Bland-Altman plots were used to determine systematic bias, reliability/variability and agreement of LNneg microarchitecture measurements.</div></div><div><h3>Results</h3><div>Linear mixed-effects models showed no systematic bias in LNneg microarchitectural features within a patient. The ICC revealed moderate variability for lymphocytes (ICC: 0.39; 95 %CI: 0.01– 0.61, p = 0.02)) and GermC (ICC: 0.50; 95 %CI: 0.22–0.68, p &lt; 0.001), and high variability for histiocytes (ICC: 0.07 (95 %CI: −0.45–0.40, p = 0.38). Bland-Altman plots showed that 5.0 % of GermC, 5.0 % of histiocytes and 8.5 % of lymphocyte measurements were outside the 95 % limits of agreement.</div></div><div><h3>Conclusions</h3><div>This is the first study to systematically assess agreement of microarchitectural features in LNneg within an individual (y)pN0 OeC patient. The absence of systematic bias supports using largest LNneg as surrogate for OeC patient’s overall anti-tumour immune response.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155818"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triptolide's impact on ACER1 signaling: Inducing autophagy for triple-negative breast cancer suppression","authors":"Lingyue Huang ,&nbsp;Rui Xue ,&nbsp;Mingfei Zhu ,&nbsp;Siyuan Xu ,&nbsp;Yuqin Luo ,&nbsp;Chuling Qin ,&nbsp;Chang Yang ,&nbsp;Lulu Jia ,&nbsp;Ke Tang ,&nbsp;Qinyou Tan","doi":"10.1016/j.prp.2025.155823","DOIUrl":"10.1016/j.prp.2025.155823","url":null,"abstract":"<div><div>Given the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (Her-2) in triple-negative breast cancer (TNBC) cells, the efficacy of targeted therapies is limited. In this study, we uncovered that triptolide (TP) effectively suppresses the migration and invasiveness of MDA-MB-231 cells by activating autophagic pathways. Western blotting analysis revealed that TP significantly reduced the expression levels of p62 protein, while simultaneously markedly increasing the expression levels of LC3B-II, BNIP3, BNIP3L, ATG5, and ULK1 proteins, strongly suggesting an enhancement of autophagic activity in the cells. Based on PCR array screening, we identified the <em>ACER1</em> gene as exhibiting notable expression alterations post-TP treatment. Overexpression of <em>ACER1</em> gene enhanced the TP-induced apoptosis in MDA-MB-231 cells and augmented the regulation of autophagy-related proteins p62 and LC3B-II, leading to an increase in autophagosome numbers and a marked reduction in cellular migration and invasiveness. Conversely, <em>ACER1</em> gene knockdown reversed these effects. In vivo experiments demonstrated that TP effectively inhibits the growth of MDA-MB-231 xenograft tumors, concurrently upregulating ACER1 and LC3B-II expression in tumor tissues, while p62 protein levels were notably decreased. Hematoxylin and eosin (H&amp;E) staining results indicated no evident toxicity in liver and kidney tissues of BALB/c mice at a TP dose of 0.4 mg/kg. This study, for the first time, elucidates a novel mechanism by which TP inhibits TNBC through an autophagic process mediated by ACER1.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155823"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067246","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":"Non-coding RNAs in Cancer: Mechanistic insights and therapeutic implications","authors":"Arjumand John ,&nbsp;Nuha Almulla ,&nbsp;Noureddine Elboughdiri ,&nbsp;Amel Gacem ,&nbsp;Krishna Kumar Yadav ,&nbsp;Anass M. Abass ,&nbsp;Mir Waqas Alam ,&nbsp;Ab Waheed Wani ,&nbsp;Showkeen Muzamil Bashir ,&nbsp;Safia Obaidur Rab ,&nbsp;Abhinav Kumar ,&nbsp;Atif Khurshid Wani","doi":"10.1016/j.prp.2024.155745","DOIUrl":"10.1016/j.prp.2024.155745","url":null,"abstract":"<div><div>Non-coding RNAs have gathered significant attention for their unique roles in biological regulation. Across a broad spectrum of developmental processes and diseases, particularly in human malignancies, ncRNAs play pivotal roles in regulatory mechanisms. MicroRNAs, long noncoding RNAs, and small nucleolar RNAs stand out among the diverse forms of ncRNAs that have been implicated in cancer. MiRNAs, classified as short non-coding RNAs, modulate gene expression by binding to messenger RNA molecules, thereby inhibiting their translation. Altered miRNA expression has been associated with the onset and progression of various malignancies, including lung, breast, and prostate cancer. In contrast, lncRNAs, characterized as longer ncRNAs, exert control over gene expression through various mechanisms, such as chromatin remodelling and gene silencing. This review offers a comprehensive examination of the numerous ncRNAs that have emerged as crucial regulators of gene expression, playing implicated roles in the initiation and progression of diverse cancers.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155745"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786399","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":"Exosomes and tumor virus interlink: A complex side of cancer","authors":"Ibrahim S. Topiwala ,&nbsp;Aparna Ramachandran ,&nbsp;Meghana Shakthi A ,&nbsp;Ranjini Sengupta ,&nbsp;Rajib Dhar ,&nbsp;Arikketh Devi","doi":"10.1016/j.prp.2024.155747","DOIUrl":"10.1016/j.prp.2024.155747","url":null,"abstract":"<div><div>Extracellular Vesicles (EVs) based cancer research reveals several complicated sides of cancer. EVs are classified as several subpopulations such as microvesicles, apoptotic bodies, and exosomes. In cancer, exosomes play a significant role as a cellular messenger in tumor development and progression. Tumor-derived exosomes (TEXs) are also a theranostic tool for cancer. Tumor virus-infected cell-derived EVs promote cancer development. Exosomes (a subpopulation of EVs) play a significant role in converting noninfecting cells to infected cells. It transports several biological active cargo (DNA, RNA, protein, and virions) towards the noninfected cells. This cellular transport enhances infection rates <em>via</em> reprogramming of noninfected cells. In this review, we explore tumor viruses, exosomes and tumor viruses interlink, the theranostic landscape of exosomes in tumor virus-associated cancer and the future orientation of exosomes-based virus oncology.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155747"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795014","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":"Enhancing the detection of clinically relevant biomarkers in advanced uterine and tubo-ovarian carcinomas through genome-wide analysis","authors":"Majd Al Assaad ,&nbsp;Kevin Hadi ,&nbsp;Jiangling Tu ,&nbsp;Max F. Levine ,&nbsp;Minal Patel ,&nbsp;Aditya Deshpande ,&nbsp;Jyothi Manohar ,&nbsp;Michael Sigouros ,&nbsp;Andrea Sboner ,&nbsp;Eloise Chapman-Davis ,&nbsp;Olivier Elemento ,&nbsp;Kevin Holcomb ,&nbsp;Baris Boyraz ,&nbsp;Juan Miguel Mosquera","doi":"10.1016/j.prp.2024.155773","DOIUrl":"10.1016/j.prp.2024.155773","url":null,"abstract":"<div><h3>Background</h3><div>Advanced-stage tube-ovarian cancers (TOC) and uterine cancers (UC) significantly contribute to cancer mortality. While surgery achieves clinical remission in most cases, recurrence often necessitates systemic therapy. Recent molecular phenotype studies have advanced targeted therapies. We employed whole genome sequencing (WGS) to investigate biomarkers in gynecologic malignancies.</div></div><div><h3>Design</h3><div>Ninety-one tumor samples (45 TOC, 46 UC) were analyzed for germline mutations, somatic driver mutations, rearrangements, genome-wide signatures, and molecular phenotypes. A WGS-based high-confidence classifier for homologous recombination deficiency (HRD) was applied. Genomic profiles were correlated with clinical outcomes.</div></div><div><h3>Results</h3><div>The HRD phenotype was identified in serous carcinoma components, with 50 % of HRD cases showing <em>BRCA1/2</em> wildtype (33 %) or variants of unknown significance (17 %). HRD correlated with better overall survival in tubo-ovarian serous carcinoma and was linked to responses to platinum therapy and PARP inhibitors. Endometrioid carcinomas showed no HRD phenotype despite <em>BRCA1/2</em> variants. <em>CDK12</em>-type genomic instability (10 %) occurred in cases with <em>CDK12</em> rearrangements, and <em>CCNE1</em> gain (8 %) was observed in <em>CCNE1</em>-amplified cases, independent of copy number. In endometrioid carcinoma, mismatch repair (MMR) deficiency single base substitution signatures, particularly SBS44, contributed to high tumor mutation burden (TMB). Ultra-high TMB was found in two cases with pathogenic <em>POLE</em> and <em>POLQ</em> mutations, exhibiting multiple SBS signatures, including MMR deficiency.</div></div><div><h3>Conclusion</h3><div>Comprehensive genomic profiling of advanced-stage TOC and UC via WGS reveals key biomarkers and therapeutic targets, enhancing diagnostic accuracy and advancing personalized medicine in gynecological cancers.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155773"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824404","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":"Tumor infiltrating lymphocytes (TILs) – Pathologia, quo vadis? – A global survey","authors":"Kristijan Skok ,&nbsp;Konstantin Bräutigam","doi":"10.1016/j.prp.2024.155775","DOIUrl":"10.1016/j.prp.2024.155775","url":null,"abstract":"<div><div>Tumor-infiltrating lymphocytes (TILs) and the tumor microenvironment have become increasingly important in cancer research, and immunotherapy has achieved major breakthroughs in improving patient outcomes. Despite the significant role of the pathologist in identifying, subtyping and reporting TILs, the implementation and assessment of TILs in pathology routine remains vague. To assess the actual use of TILs in routine clinical practice, a formal standardized questionnaire was disseminated on two social media platforms (“X” and LinkedIn) and by email in June 2024. Based on the results, we conducted a literature review on TILs via Medline/Pubmed in the two most scored and reported entities, namely malignant melanoma and colorectal cancer (CRC). 77 participants from 24 different countries around the world, mostly pathologists (n = 63, 82.0 %), completed the survey. More than half of the participants do not assess or report TILs in their daily (clinical) practice, a trend consistent across the countries included in the study. A variety of methods are used to report TILs, ranging from Artificial Intelligence (AI)-based scoring algorithms to quantification by eyeballing. Despite recognizing the importance of TIL assessment in clinical routine, many participants find it time-consuming and express a strong preference for AI-based quantification. Our survey reflects the perspective of mostly early career pathologists who recognize the importance of TILs in cancer but face challenges in implementation. The development of AI tools and consensus guidelines could alleviate these barriers. In addition, increasing the visibility and understanding of the role of pathologists within the medical community remains critical.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155775"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular and pathological landscape of the AT-rich interaction domain 1A (ARID1A) mutation in hepatocellular carcinoma","authors":"Junfeng Li ,&nbsp;Yuxia Fu ,&nbsp;Hongchuan Zhang ,&nbsp;Hong Ma","doi":"10.1016/j.prp.2024.155763","DOIUrl":"10.1016/j.prp.2024.155763","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, with complex etiological factors and a diverse genetic landscape. Among the critical genetic mutations in HCC, the AT-rich interaction domain 1 A (ARID1A) gene, a key component of the SWI/SNF chromatin remodeling complex, stands out due to its significant role in both tumor suppression and oncogenesis. This review comprehensively examines the molecular and pathological impacts of ARID1A mutations in HCC. ARID1A mutations, which occur in approximately 7.9 % of HCC cases, predominantly involve truncating mutations leading to loss of function. These mutations are associated with various aggressive cancer features, including larger tumor size, higher rates of metastasis, and poor prognosis. The dual role of ARID1A in HCC is context-dependent, acting as a tumor suppressor by regulating cell cycle control, DNA damage repair, and gene expression, while also displaying oncogenic properties in specific contexts by promoting early tumorigenesis through oxidative stress pathways. Understanding the molecular mechanisms of ARID1A, including its interactions with key cellular pathways such as PI3K/AKT/mTOR, β-catenin, and PD-L1, provides insights into its complex role in HCC pathogenesis. Furthermore, ARID1A's impact on cancer stem cell maintenance, metabolic reprogramming, and immune evasion underscores its potential as a therapeutic target. This review highlights the need for context-specific therapeutic strategies targeting ARID1A, which could lead to more effective treatments for HCC, addressing both its tumor-suppressive and oncogenic activities.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155763"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872738","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}