The Journal of Pathology最新文献

{"title":"Super resolution of pathology images with hierarchical feature integration and local image patterns.","authors":"Feng Xu, Lei Li, Shuyang Wang, Ren Ling, Xie Zhang, Xi Deng, Mengzhe Zhou, Jin Ling, Chaofei Gao","doi":"10.1002/path.6482","DOIUrl":"https://doi.org/10.1002/path.6482","url":null,"abstract":"<p><p>Recent advancements in pathological imaging have facilitated single-cell and subcellular-level analysis based on high-resolution images for tumor subtyping, cytomorphological assessment, and infection detection. As high-resolution imaging is often limited by cost, super-resolution methods provide a practical alternative with only low-resolution data. However, existing methods generally suffer from artifacts, oversmoothing, and slow inference speed. In this study, we developed a hierarchal deep learning framework based on local pathological image patterns, named Hierarchical Local Image Patterns (HLIP), to achieve accurate, high-fidelity, and real-time super resolution with flexible magnifications. HLIP integrates semantic features with both pixel- and morphology-level features and reconstructs super-resolution images by the recognized local pathological image patterns. Benchmark analysis showed HLIP achieved the best performance and robustness on both internal and external test datasets. The generated super-resolution images contain abundant pathological details and maintain high fidelity. HLIP can be used for the enhancement of other models across multiple clinical scenarios, including gland segmentation, cell segmentation, Helicobacter pylori detection, and therapy response prediction. With its superior performance in pathology image super resolution, HLIP offers a versatile tool for image preprocessing in computer-aided systems, thereby supporting accurate diagnosis in clinical practice. © 2025 The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to ‘Development and characterization of improved unifocal primary mouse lung cancer models with metastatic potential’","authors":"","doi":"10.1002/path.6489","DOIUrl":"10.1002/path.6489","url":null,"abstract":"<p>\u0000 <span>Ana-Rita Pedrosa</span>, <span>Alejandro Castillo-Kauil</span>, <span>Yuliia Kravchuk</span>, <span>Louise Reynolds</span>, <span>Bruce Williams</span>, <span>David Moore</span>, <span>Cameron Lang</span>, <span>Srinivas Allanki</span>, <span>Eleni Maniati</span>, <span>Alexandros Hardas</span>, <span>Jozafina Haj</span>, <span>Rebecca Drake</span>, <span>Julie Cleaver</span>, <span>Julie Foster</span>, <span>Jana Kim</span>, <span>Ester Stern</span>, <span>Jane Sosabowski</span>, <span>Gilbert O. Fruhwirth</span>, <span>Erik Sahai</span>, <span>Ori Wald</span> and <span>Kairbaan Hodivala-Dilke</span>. <i>J Pathol</i> <span>2025</span>; <span>266</span><b>:</b> <span>405</span>–<span>420</span>; https://doi.org/10.1002/path.6435\u0000 </p><p>The senior author has informed the editors of three errors in the Acknowledgements section of this article, first published on 18 June 2025 in Wiley Online Library (wileyonlinelibrary.com).</p><p>First, the affiliation of the technicians was given incorrectly. The correct affiliation is HEFCE-funded specialist animal technicians.</p><p>Second, the Animal Technician Service (ATS) was stated incorrectly. The correct affiliation is the BCI Animal Technician Service (ATS).</p><p>Third, the name of the second technician was spelt incorrectly. The correct spelling is Kaylee O'Brien Perry.</p><p>The original sentence read:</p><p>“The authors would also like to thank the BSU technicians Julie Holdsworth and Kaylee Perry and the Animal Technician Service (ATS) for their support in all of the mouse studies.”</p><p>The corrected sentence should read:</p><p>“The authors would also like to thank the HEFCE-funded specialist animal technicians Julie Holdsworth and Kaylee O'Brien Perry, and the BCI Animal Technician Service (ATS), for their support in all of the mouse studies.”</p><p>The authors apologise for these errors and for any inconvenience caused.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"267 3","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/path.6489","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA-hypermethylated human gastric cancer circumvents apoptosis in the absence of TP53 mutation.","authors":"Yasunobu Mano, Keisuke Matsusaka, Motoaki Seki, Kazuko Kita, Masaki Fukuyo, Bahityar Rahmutulla, Genki Usui, Ryoji Fujiki, Masayuki Urabe, Hiroyuki Abe, Hisahiro Matsubara, Tetsuo Ushiku, Yasuyuki Seto, Masashi Fukayama, Atsushi Kaneda","doi":"10.1002/path.6480","DOIUrl":"https://doi.org/10.1002/path.6480","url":null,"abstract":"<p><p>p53 is one of the most important tumour suppressors exerting antitumour effects primarily via apoptosis. TP53 mutations are common in gastric tumorigenesis; however, nearly half of the gastric cancers (GCs) remain wildtype TP53 (TP53_WT). We investigated epigenetic/genetic profiles of GCs and the carcinogenic mechanisms underlying GCs with TP53_WT. Comprehensive DNA methylation analysis revealed four DNA methylation epigenotypes (MEs) in GCs, namely, high ME (HME), extremely HME (E-HME), low ME (LME), and extremely LME (E-LME). E-HME matched Epstein-Barr virus (EBV)-positive GC (E-HME/EBV). HME can be further categorised into MLH1-deficient (HME_MLH1(-)) and -proficient cases. The Cancer Genome Atlas data confirmed that HME_MLH1(-)/microsatellite instability (MSI) and E-HME/EBV cases significantly retained TP53_WT and had higher MDM2 expression levels than other MEs. We hypothesised that apoptosis pathways in TP53_WT GC may be suppressed post-transcriptionally by activated MDM2. Short hairpin RNA-mediated MDM2 knockdown and the p53-MDM2 inhibitors, nutlin-3 and RG7388, induced apoptosis in TP53_WT GC cells, indicating that activated MDM2 suppressed p53 protein levels and thereby attenuated the downstream p53 pathway activation, which was restored upon MDM2 knockdown or inhibitor treatment. Collectively, DNA-hypermethylated GC cases, HME_MLH1(-)/MSI and E-HME/EBV, follow a unique carcinogenic pathway to evade apoptosis in the absence of TP53 mutation, potentially making them responsive to therapeutic strategies that function primarily through the p53 pathway. © 2025 The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutation profiling in differential diagnosis between TdT-positive high-grade/large B-cell lymphoma and B-lymphoblastic leukaemia/lymphoma.","authors":"Maria-Myrsini Tzioni, Francesco Cucco, Lívia Rásó-Barnett, Zi Chen, Andrew Wotherspoon, Katrin S Kurz, Ewelina Madej, Jasmine Makker, Anna E Strazda, Fang Guo, Caoimhe Egan, Elizabeth Soilleux, Liz Hook, Laszlo Krenacs, Julia T Geyer, Camille Laurent, Luc Xerri, Lenaïg Mescam, Lukas Plank, Lise Mette Rahbek Gjerdrum, Nicolas Lopez-Hisijos, Timothy Greiner, Joseph Khoury, Wolfram Klapper, Ilske Oschlies, Andreas Rosenwald, German Ott, Ming-Qing Du","doi":"10.1002/path.6476","DOIUrl":"https://doi.org/10.1002/path.6476","url":null,"abstract":"<p><p>Terminal deoxynucleotidyl transferase (TdT) is occasionally expressed in large B-cell lymphoma (LBCL), and this causes difficulty in differential diagnosis from B-lymphoblastic leukaemia/lymphoma (B-ALL/LBL). We reviewed 31 cases of TdT-positive LBCL and B-ALL/LBL, and their final diagnosis included 19 diffuse large/high-grade BCLs with MYC and BCL2 rearrangements (five DLBCL-MYC/BCL2, 14 HGBCL-MYC/BCL2), three DLBCL not otherwise specified (NOS), three HGBCL-NOS, four B-ALL/LBL, and two unclassifiable cases. TdT was variably expressed in all these cases, without any clear demarcation among different groups. Loss or partial loss of CD20 expression was seen in 13/17 DLBCL/HGBCL-MYC/BCL2, 2/3 HGBCL-NOS, and 2/2 unclassified, albeit not in DLBCL-NOS. Expression of BCL6 and/or MUM1 was seen in 3/4 B-ALL/LBLs and 2/2 unclassified. Next-generation sequencing revealed characteristic mutations associated with follicular lymphoma and its high-grade transformation in each DLBCL/HGBCL-MYC/BCL2, and also frequent variants in genes targeted by somatic hypermutation (SHM) in almost all DLBCL/HGBCL-MYC/BCL2, DLBCL-NOS, and HGBCL-NOS but one case. In contrast, such mutations were absent in B-ALL/LBL. There were no pathognomonic mutations in the two unclassifiable cases, although one showed a moderate level of somatic mutations in its rearranged IGHV. Furthermore, in three cases of TdT-positive HGBCL-MYC/BCL2, studies of previous or concurrent follicular lymphoma demonstrated their divergent evolution from an IGH::BCL2-positive cell population following acquisition of MYC translocation. In conclusion, mutation profiling analysis including the SHM target genes is highly valuable in the differential diagnosis between TdT-positive LBCL and B-ALL/LBL. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145230978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Androgen receptor-mediated regulation of BRCA1 modulates the antioxidant defense in prostate cancer.","authors":"Saiganesh Sriraman, Verneri Virtanen, Antti Kukkula, Mervi Toriseva, Anni Lumiainen, Gun West, Matti Poutanen, Pekka Taimen, Maria Sundvall","doi":"10.1002/path.6468","DOIUrl":"https://doi.org/10.1002/path.6468","url":null,"abstract":"<p><p>Lethal prostate cancer (PCa) is a genetically heterogeneous disease characterized by evolving androgen receptor (AR) signaling, eventually culminating in castration resistance. The tumor suppressor gene BRCA1 has multiple functions that include secondary processes cooperating with its main function as a caretaker of genomic integrity. BRCA1 is often mutated in breast and ovarian cancer, but BRCA1 mutations are also associated with PCa, although they are less frequently observed. Most PCa patients do not, however, carry BRCA1 mutations, and interestingly, it has been shown that BRCA1 expression is enriched in castration-resistant PCa. In this study we elucidated the prostate tissue-specific role of the BRCA1 protein. Although the regulation of DNA damage response genes has been studied in PCa, comprehensive analyses of BRCA1 regulation in the context of androgen signaling are lacking. Our results indicate that BRCA1 is dynamically regulated by AR signaling and that activation of AR via its natural ligand, dihydrotestosterone, represses BRCA1 expression. Our analyses both in vitro and of patient samples and mouse xenografts showed that BRCA1 expression was induced and sustained after androgen deprivation. Moreover, we observed that oxidative stress-related pathways were regulated by BRCA1 in PCa cells and that androgen deprivation therapy-induced activation of BRCA1 supported the function of NRF2, the master regulator of antioxidant defense, and a known interactor of BRCA1. Impaired NRF2 activity, in the absence of BRCA1, decreased growth in a 3D environment. Our findings shed light on the functional role of BRCA1 protein in PCa and suggest that BRCA1 is regulated by the evolving AR signaling state during PCa progression. Thus, AR-mediated suppression of BRCA1 accumulates oncogenic alterations in the early phases of PCa tumor progression and safeguards from excessive reactive oxygen species (ROS) when upregulated during androgen deprivation therapy. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145230994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of SARS-CoV-2 entry-associated proteins in COPD airways: an immunohistochemical study.","authors":"Larissa E Vlaming-van Eijk, Zarlasht Sarsam, Janna Bakker, Marjan Reinders-Luinge, Corry-Anke Brandsma, Wim Timens","doi":"10.1002/path.6477","DOIUrl":"https://doi.org/10.1002/path.6477","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19) is of special concern to patients with chronic obstructive pulmonary disease (COPD), given their susceptibility to exacerbations caused by respiratory tract infections. As the susceptibility of acquiring a SARS-CoV-2 infection in COPD remains unclear, this study explored the airway expression of SARS-CoV-2 entry-associated proteins in the lungs of COPD patients in comparison to non-COPD controls. Immunohistochemical staining of lung tissue was performed to investigate the expression profiles of SARS-CoV-2 entry-associated proteins in the bronchial epithelium of 27 COPD patients and 40 non-COPD controls. In addition, the associations between these expression profiles with lung function in COPD patients and smoking status in non-COPD controls were examined. COPD patients demonstrated smoking-independent lower expression of HSPA5, NRP1, BSG, TMPRSS2, and ITGB6 in airway epithelium as compared to non-COPD controls. No significant differences were observed for Furin, CTSL, ADAM17, and ITGA5. BSG percentage area expression was significantly negatively associated with lung function in COPD patients. Moreover, the study revealed smoking-associated differences for Furin, HSPA5, ADAM17, BSG, ITGA5, and ITGB6 within non-COPD controls, with lower airway epithelial expression (except for Furin) in ever-smokers than in never-smokers. To conclude, this study showed a lower expression of a specific set of SARS-CoV-2 entry-associated proteins in the bronchial epithelium of COPD patients compared with non-COPD controls, while other factors showed similar expression levels. The consequences of these findings on COVID-19 susceptibility remain uncertain. Although reduced expression of entry factors may suggest less cellular availability for viral entry, it could be speculated that the similar expression levels of other factors, together with impaired airway clearance in COPD, may still facilitate infection, thereby providing potential mechanistic insight into COVID-19 susceptibility in this patient population. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145230931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KMT2D deficiency potentiates antitumor immunity and sensitizes immune checkpoint blockade in urologic cancers.","authors":"Yuedian Ye, Yuanpeng Liao, Yifan Zhang, Jianqiang Zhang, Mayao Luo, Qiao Yang, Qiliang Zhai, Zhuofan Xu, Yutong Wang, Haoran Wen, Chenwei Wu, Yang Qiu, Shidong Lv, Qiang Wei","doi":"10.1002/path.6481","DOIUrl":"https://doi.org/10.1002/path.6481","url":null,"abstract":"<p><p>Immune checkpoint blockade (ICB) therapy has made remarkable advances in cancer treatment. However, the overall response rate remains limited. Here, we aim to explore the role of histone 3 lysine 4 mono-methyltransferase KMT2D in tumor immune response and improve the efficacy of ICB. We developed a patient-derived urologic tumor fragment (PDUTF) platform comprising 56 tumors and constructed three major urological tumor tissue microarrays from 356 patients. Analyzed using the PDUTF platform and tissue microarrays (TMAs), we found that tumors with KMT2D deficiency were associated with enhanced T-cell activation in response to anti-PD-1 therapy and exhibited increased T-cell infiltration. Subsequently, T-cell migration and T-cell-mediated tumor cell killing assays revealed that the deletion of KMT2D in cancer cells promoted CD8⁺ T-cell migration and cytotoxicity against tumor cells. Mechanistically, the loss of KMT2D enhanced antitumor immunity by promoting chemokine-mediated recruitment of T cells both in vitro and in vivo. Finally, the small-molecule inhibitor MI-503 combined with anti-PD-1 therapy suppressed tumor growth on the PDUTF platform. Collectively, KMT2D deficiency sensitizes tumor cells to ICB, and inhibiting KMT2D may represent a promising approach in combination with ICB to improve patient prognosis. © 2025 The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145230948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing homebrew AI in diagnostic practice: opportunities and barriers^†.","authors":"Zaid H Khoury, Ahmed S Sultan","doi":"10.1002/path.6483","DOIUrl":"https://doi.org/10.1002/path.6483","url":null,"abstract":"<p><p>In a recent issue of The Journal of Pathology, Calderaro et al present a timely and persuasive argument advocating for the integration of homebrew artificial intelligence (AI) models in diagnostic pathology. Their article is a robust defense of local model development within pathology departments as a pathway to democratizing digital diagnostics. This commentary expands on their premise, critically examining the real-world implications, practical limitations, and unmet needs of practicing pathologists. The commentary outlines both the opportunities and challenges for the widespread adoption of homebrew AI in pathology practice. Without institutional backing, digital infrastructure, and sustained training efforts, the promise of homebrew AI may falter. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated mitochondrial energy metabolism drives the progression of mucosal field effects to invasive bladder cancer","authors":"Sangkyou Lee,&nbsp;Sung Yun Jung,&nbsp;Pawel Kuś,&nbsp;Jolanta Bondaruk,&nbsp;June Goo Lee,&nbsp;Roman Jaksik,&nbsp;Nagireddy Putluri,&nbsp;Khanh N Dinh,&nbsp;David Cogdell,&nbsp;Huiqin Chen,&nbsp;Yishan Wang,&nbsp;Jiansong Chen,&nbsp;Neema Navai,&nbsp;Colin Dinney,&nbsp;Cathy Mendelsohn,&nbsp;David McConkey,&nbsp;Richard R Behringer,&nbsp;Charles C Guo,&nbsp;Peng Wei,&nbsp;Marek Kimmel,&nbsp;Bogdan Czerniak","doi":"10.1002/path.6474","DOIUrl":"10.1002/path.6474","url":null,"abstract":"<p>Multiplatform mutational and gene expression profiling complemented with proteomic and metabolomic spatial mapping were used on the whole-organ scale to identify the molecular profile of bladder cancer evolution from field effects. Analysis of the mutational landscape identified three types of mutations, referred to as α, β, and γ. Time modeling of the mutations revealed that carcinogenesis may span 30 years and can be divided into dormant and progressive phases. The α mutations developed in the dormant phase. The progressive phase lasted 5 years and was signified by expanding β mutations, but it was driven to invasive cancer by γ mutations. The mutational landscape emerged on a background of disorganized urothelial differentiation, activated epithelial-mesenchymal transition, and enhanced immune infiltration with T-cell exhaustion. Complex dysregulation of mitochondrial energy metabolism with downregulation of oxidative phosphorylation emerged as the leading mechanism driving the progression of mucosal field effects to invasive cancer. © 2025 The Author(s). <i>The Journal of Pathology</i> published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"267 3","pages":"329-346"},"PeriodicalIF":5.2,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/path.6474","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracing metastatic spread in pediatric solid tumors using copy number and targeted deep sequencing","authors":"Natalie Andersson,&nbsp;Michele Ferro,&nbsp;Caroline Jansson,&nbsp;Subhayan Chattopadhyay,&nbsp;Jenny Karlsson,&nbsp;David Gisselsson","doi":"10.1002/path.6472","DOIUrl":"10.1002/path.6472","url":null,"abstract":"<p>The most common cause of death in pediatric cancer patients is a treatment-resistant tumor, compounded by metastatic spread, making surgery, radiation therapy, and chemotherapy unfeasible as curative treatment options. However, the mechanisms behind metastatic spread in pediatric tumors remain largely unexplored. We conducted whole-genome copy number profiling on 171 primary tumor and metastases samples from 17 patients with neuroblastoma, Wilms tumor, or gonadal tumors, and performed targeted deep sequencing on a subset. Phylogenetic reconstruction enabled spatiotemporal tracking of subclones. In total, 11 of 17 patients displayed at least one metastasis arising earlier, defined as occurring before the most recent common ancestor in the primary tumor. In eight patients, metastatic spread was observed several times during tumor evolution, with different subclones from the same primary tumor having metastatic capability, even colonizing the same site. Strikingly, dissemination between metastases (intermetastatic spread) occurred in eight of nine patients with metastases in at least two different sites, indicating that this is a common phenomenon in pediatric malignancy. © 2025 The Author(s). <i>The Journal of Pathology</i> published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"267 3","pages":"347-365"},"PeriodicalIF":5.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/path.6472","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}