The Journal of Pathology最新文献

{"title":"List of Reviewers","authors":"","doi":"10.1002/path.6269","DOIUrl":"https://doi.org/10.1002/path.6269","url":null,"abstract":"<p>The high quality of manuscripts published in <i>The Journal of Pathology</i> largely relies on the standards set by our expert reviewers. <i>The Journal of Pathology</i> wishes to thank the following 541 individuals who assisted by reviewing articles for the Journal in 2023 (affiliations shown are those currently held in our system).</p><p>Catherine Abbott, University of Edinburgh, Edinburgh, UK.</p><p>Balazs Acs, Karolinska Institutet, Stockholm, Sweden.</p><p>Alejandro Adam, Albany Medical College, Albany, NY, USA.</p><p>Rosalyn Adam, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.</p><p>Rahul Aggarwal, University of California San Francisco, San Francisco, CA, USA.</p><p>Saif S Ahmad, CRUK Cambridge Centre, Cambridge, UK.</p><p>Jared Ahrendsen, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.</p><p>Katherine M Aird, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.</p><p>Rannar Airik, Medizinische Hochschule Hannover, Hannover, Germany.</p><p>Hikmat Al-Ahmadie, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.</p><p>Hana Algul, Klinikum rechts der Isar der Technischen Universitat München, München, Germany.</p><p>Malcolm Alison, Barts and the London School of Medicine & Dentistry, The Royal London Hospital, London, UK.</p><p>Alhadi Almangush, Helsingin yliopisto Haartman-instituutti, Helsinki, Finland.</p><p>Kristian Almstrup, Rigshospitalet, Kobenhavn, Denmark.</p><p>Cristina Amaral, Faculty of Pharmacy, University of Porto, Porto, Portugal.</p><p>Brage S Andresen, University of Southern Denmark, Odense, Denmark.</p><p>Corrado Angelini, University of Padova, Padova, Veneto, Italy.</p><p>David Assis, Yale School of Medicine, New Haven, CT, USA.</p><p>Radhika Atit, Case Western Reserve University, Cleveland, OH, USA.</p><p>Matias Avila, University of Navarra, Pamplona, Spain.</p><p>George Baillie, University of Glasgow, Glasgow, UK.</p><p>Holly Barker, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.</p><p>Sonali Barwe, Nemours Children's Hospital Delaware, Wilmington, DE, USA.</p><p>Ali Bashashati, British Columbia Cancer Agency, Vancouver, BC, Canada.</p><p>David P Basile, Indiana University School of Medicine, Indianapolis, IN, USA.</p><p>M Albert Basson, Kings College London, London, UK.</p><p>Adrian Bateman, University Hospital Southampton NHS Foundation Trust, Southampton, UK.</p><p>Daniel Baumhoer, University Hospital Basel, Basel, Switzerland.</p><p>Jan Becker, University Hospital of Cologne, Cologne, Germany.</p><p>Andrew Beggs, University of Birmingham, Birmingham, UK.</p><p>Jurgen Behrens, University Erlangen, Erlangen, Germany.</p><p>Hannah Beird, University of Texas MD Anderson Cancer Center, Houston, TX, USA.</p><p>Susan Bellis, University of Alabama, Birmingham, AL, USA.</p><p>Dorina Belotti, Mario Negri Institute for Pharmacological Research, Bergamo, Italy.</p><p>Don Benjamin, University of Basel, Basel, Switzerland.</p><p>J","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"262 4","pages":"529-538"},"PeriodicalIF":7.3,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6269","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140031847","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":"AI-guided histopathology predicts brain metastasis in lung cancer patients","authors":"Haowen Zhou,&nbsp;Mark Watson,&nbsp;Cory T Bernadt,&nbsp;Steven (Siyu) Lin,&nbsp;Chieh-yu Lin,&nbsp;Jon H Ritter,&nbsp;Alexander Wein,&nbsp;Simon Mahler,&nbsp;Sid Rawal,&nbsp;Ramaswamy Govindan,&nbsp;Changhuei Yang,&nbsp;Richard J Cote","doi":"10.1002/path.6263","DOIUrl":"10.1002/path.6263","url":null,"abstract":"<p>Brain metastases can occur in nearly half of patients with early and locally advanced (stage I–III) non-small cell lung cancer (NSCLC). There are no reliable histopathologic or molecular means to identify those who are likely to develop brain metastases. We sought to determine if deep learning (DL) could be applied to routine H&amp;E-stained primary tumor tissue sections from stage I–III NSCLC patients to predict the development of brain metastasis. Diagnostic slides from 158 patients with stage I–III NSCLC followed for at least 5 years for the development of brain metastases (Met⁺, 65 patients) versus no progression (Met⁻, 93 patients) were subjected to whole-slide imaging. Three separate iterations were performed by first selecting 118 cases (45 Met⁺, 73 Met⁻) to train and validate the DL algorithm, while 40 separate cases (20 Met⁺, 20 Met⁻) were used as the test set. The DL algorithm results were compared to a blinded review by four expert pathologists. The DL-based algorithm was able to distinguish the eventual development of brain metastases with an accuracy of 87% (<i>p</i> &lt; 0.0001) compared with an average of 57.3% by the four pathologists and appears to be particularly useful in predicting brain metastases in stage I patients. The DL algorithm appears to focus on a complex set of histologic features. DL-based algorithms using routine H&amp;E-stained slides may identify patients who are likely to develop brain metastases from those who will remain disease free over extended (&gt;5 year) follow-up and may thus be spared systemic therapy. © 2024 The Authors. <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":"263 1","pages":"89-98"},"PeriodicalIF":7.3,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140020475","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":"List of Reviewers","authors":"","doi":"10.1002/path.6269","DOIUrl":"https://doi.org/10.1002/path.6269","url":null,"abstract":"&lt;p&gt;The high quality of manuscripts published in &lt;i&gt;The Journal of Pathology&lt;/i&gt; largely relies on the standards set by our expert reviewers. &lt;i&gt;The Journal of Pathology&lt;/i&gt; wishes to thank the following 541 individuals who assisted by reviewing articles for the Journal in 2023 (affiliations shown are those currently held in our system).&lt;/p&gt;&lt;p&gt;Catherine Abbott, University of Edinburgh, Edinburgh, UK.&lt;/p&gt;&lt;p&gt;Balazs Acs, Karolinska Institutet, Stockholm, Sweden.&lt;/p&gt;&lt;p&gt;Alejandro Adam, Albany Medical College, Albany, NY, USA.&lt;/p&gt;&lt;p&gt;Rosalyn Adam, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.&lt;/p&gt;&lt;p&gt;Rahul Aggarwal, University of California San Francisco, San Francisco, CA, USA.&lt;/p&gt;&lt;p&gt;Saif S Ahmad, CRUK Cambridge Centre, Cambridge, UK.&lt;/p&gt;&lt;p&gt;Jared Ahrendsen, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.&lt;/p&gt;&lt;p&gt;Katherine M Aird, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.&lt;/p&gt;&lt;p&gt;Rannar Airik, Medizinische Hochschule Hannover, Hannover, Germany.&lt;/p&gt;&lt;p&gt;Hikmat Al-Ahmadie, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.&lt;/p&gt;&lt;p&gt;Hana Algul, Klinikum rechts der Isar der Technischen Universitat München, München, Germany.&lt;/p&gt;&lt;p&gt;Malcolm Alison, Barts and the London School of Medicine &amp; Dentistry, The Royal London Hospital, London, UK.&lt;/p&gt;&lt;p&gt;Alhadi Almangush, Helsingin yliopisto Haartman-instituutti, Helsinki, Finland.&lt;/p&gt;&lt;p&gt;Kristian Almstrup, Rigshospitalet, Kobenhavn, Denmark.&lt;/p&gt;&lt;p&gt;Cristina Amaral, Faculty of Pharmacy, University of Porto, Porto, Portugal.&lt;/p&gt;&lt;p&gt;Brage S Andresen, University of Southern Denmark, Odense, Denmark.&lt;/p&gt;&lt;p&gt;Corrado Angelini, University of Padova, Padova, Veneto, Italy.&lt;/p&gt;&lt;p&gt;David Assis, Yale School of Medicine, New Haven, CT, USA.&lt;/p&gt;&lt;p&gt;Radhika Atit, Case Western Reserve University, Cleveland, OH, USA.&lt;/p&gt;&lt;p&gt;Matias Avila, University of Navarra, Pamplona, Spain.&lt;/p&gt;&lt;p&gt;George Baillie, University of Glasgow, Glasgow, UK.&lt;/p&gt;&lt;p&gt;Holly Barker, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.&lt;/p&gt;&lt;p&gt;Sonali Barwe, Nemours Children's Hospital Delaware, Wilmington, DE, USA.&lt;/p&gt;&lt;p&gt;Ali Bashashati, British Columbia Cancer Agency, Vancouver, BC, Canada.&lt;/p&gt;&lt;p&gt;David P Basile, Indiana University School of Medicine, Indianapolis, IN, USA.&lt;/p&gt;&lt;p&gt;M Albert Basson, Kings College London, London, UK.&lt;/p&gt;&lt;p&gt;Adrian Bateman, University Hospital Southampton NHS Foundation Trust, Southampton, UK.&lt;/p&gt;&lt;p&gt;Daniel Baumhoer, University Hospital Basel, Basel, Switzerland.&lt;/p&gt;&lt;p&gt;Jan Becker, University Hospital of Cologne, Cologne, Germany.&lt;/p&gt;&lt;p&gt;Andrew Beggs, University of Birmingham, Birmingham, UK.&lt;/p&gt;&lt;p&gt;Jurgen Behrens, University Erlangen, Erlangen, Germany.&lt;/p&gt;&lt;p&gt;Hannah Beird, University of Texas MD Anderson Cancer Center, Houston, TX, USA.&lt;/p&gt;&lt;p&gt;Susan Bellis, University of Alabama, Birmingham, AL, USA.&lt;/p&gt;&lt;p&gt;Dorina Belotti, Mario Negri Institute for Pharmacological Research, Bergamo, Italy.&lt;/p&gt;&lt;p&gt;Don Benjamin, University of Basel, Basel, Switzerland.&lt;/p&gt;&lt;p&gt;J","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"262 4","pages":"529-538"},"PeriodicalIF":7.3,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6269","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140031855","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":"KAT8/SIRT7-mediated Fascin-K41 acetylation/deacetylation regulates tumor metastasis in esophageal squamous cell carcinoma","authors":"Da-Jia Li,&nbsp;Yin-Wei Cheng,&nbsp;Jin-Mei Pan,&nbsp;Zhen-Chang Guo,&nbsp;Shao-Hong Wang,&nbsp;Qing-Feng Huang,&nbsp;Ping-Juan Nie,&nbsp;Wen-Qi Shi,&nbsp;Xiu-E Xu,&nbsp;Bing Wen,&nbsp;Jin-Ling Zhong,&nbsp;Zhi-Da Zhang,&nbsp;Zhi-Yong Wu,&nbsp;Hui Zhao,&nbsp;Lian-Di Liao,&nbsp;Jian-Yi Wu,&nbsp;Kai Zhang,&nbsp;Geng Dong,&nbsp;En-Min Li,&nbsp;Li-Yan Xu","doi":"10.1002/path.6261","DOIUrl":"10.1002/path.6261","url":null,"abstract":"<p>Fascin actin-bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F-actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin-mediated F-actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD-dependent protein deacetylase sirtuin (SIRT) 7-mediated deacetylation of Fascin-K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin-K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin-K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP-G2-044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP-G2-044 may be more suitable for patients with low levels of Fascin-K41 acetylation, but not suitable for patients with high levels of Fascin-K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"263 1","pages":"74-88"},"PeriodicalIF":7.3,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139970359","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":"Serine/threonine-protein kinase D2-mediated phosphorylation of DSG2 threonine 730 promotes esophageal squamous cell carcinoma progression","authors":"Yin-Qiao Liu,&nbsp;Yi-Wei Xu,&nbsp;Zheng-Tan Zheng,&nbsp;Die Li,&nbsp;Chao-Qun Hong,&nbsp;Hao-Qiang Dai,&nbsp;Jun-Hao Wang,&nbsp;Ling-Yu Chu,&nbsp;Lian-Di Liao,&nbsp;Hai-Ying Zou,&nbsp;En-Min Li,&nbsp;Jian-Jun Xie,&nbsp;Wang-Kai Fang","doi":"10.1002/path.6264","DOIUrl":"10.1002/path.6264","url":null,"abstract":"<p>Desmoglein-2 (DSG2) is a transmembrane glycoprotein belonging to the desmosomal cadherin family, which mediates cell–cell junctions; regulates cell proliferation, migration, and invasion; and promotes tumor development and metastasis. We previously showed serum DSG2 to be a potential biomarker for the diagnosis of esophageal squamous cell carcinoma (ESCC), although the significance and underlying molecular mechanisms were not identified. Here, we found that DSG2 was increased in ESCC tissues compared with adjacent tissues. In addition, we demonstrated that DSG2 promoted ESCC cell migration and invasion. Furthermore, using interactome analysis, we identified serine/threonine-protein kinase D2 (PRKD2) as a novel DSG2 kinase that mediates the phosphorylation of DSG2 at threonine 730 (T730). Functionally, DSG2 promoted ESCC cell migration and invasion dependent on DSG2-T730 phosphorylation. Mechanistically, DSG2 T730 phosphorylation activated EGFR, Src, AKT, and ERK signaling pathways. In addition, DSG2 and PRKD2 were positively correlated with each other, and the overall survival time of ESCC patients with high DSG2 and PRKD2 was shorter than that of patients with low DSG2 and PRKD2 levels. In summary, PRKD2 is a novel DSG2 kinase, and PRKD2-mediated DSG2 T730 phosphorylation promotes ESCC progression. These findings may facilitate the development of future therapeutic agents that target DSG2 and DSG2 phosphorylation. © 2024 The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"263 1","pages":"99-112"},"PeriodicalIF":7.3,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139970360","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":"Hourglass, a compass navigating global and regional heterogeneity of pancreatic cancer†","authors":"Derya Bakırdöğen,&nbsp;Kıvanç Görgülü,&nbsp;Hana Algül","doi":"10.1002/path.6268","DOIUrl":"10.1002/path.6268","url":null,"abstract":"<p>Advances in the digital pathology field have facilitated the characterization of histology samples for both clinical and preclinical research. However, uncovering subtle correlations between bioimaging, clinical and molecular parameters requires extensive statistical analysis. As a user-friendly software, Hourglass, simplifies multiparametric dataset analysis through intuitive data visualization and statistical tools. Systemic analysis of interleukin-6 (IL-6)/pStat3 signaling pathway through Hourglass revealed differences in regional immune cell composition within tumors. Moreover, these regional disparities were partially mediated by sex. Overall, Hourglass simplifies information extraction from complex datasets, resolving overlooked regional and global spatial tumor differences. © 2024 The Authors. <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":"263 1","pages":"5-7"},"PeriodicalIF":7.3,"publicationDate":"2024-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139969359","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":"Cellular and molecular characteristics of stromal Lkb1 deficiency-induced gastrointestinal polyposis based on single-cell RNA sequencing","authors":"Zhaohua Cai,&nbsp;Yangjing Jiang,&nbsp;Huan Tong,&nbsp;Min Liang,&nbsp;Yijie Huang,&nbsp;Liang Fang,&nbsp;Feng Liang,&nbsp;Yunwen Hu,&nbsp;Xin Shi,&nbsp;Jian Wang,&nbsp;Zi Wang,&nbsp;Qingqi Ji,&nbsp;Huanhuan Huo,&nbsp;Linghong Shen,&nbsp;Ben He","doi":"10.1002/path.6259","DOIUrl":"10.1002/path.6259","url":null,"abstract":"<p>Liver kinase B1 (Lkb1), encoded by serine/threonine kinase (<i>Stk11</i>), is a serine/threonine kinase and tumor suppressor that is strongly implicated in Peutz–Jeghers syndrome (PJS). Numerous studies have shown that mesenchymal-specific Lkb1 is sufficient for the development of PJS-like polyps in mice. However, the cellular origin and components of these Lkb1-associated polyps and underlying mechanisms remain elusive. In this study, we generated tamoxifen-inducible <i>Lkb1</i>^{<i>flox/flox</i>};<i>Myh11-Cre/ERT2</i> and <i>Lkb1</i>^{<i>flox/flox</i>};<i>PDGFRα-Cre/ERT2</i> mice, performed single-cell RNA sequencing (scRNA-seq) and imaging-based lineage tracing, and aimed to investigate the cellular complexity of gastrointestinal polyps associated with PJS. We found that <i>Lkb1</i>^{<i>flox/+</i>};<i>Myh11-Cre/ERT2</i> mice developed gastrointestinal polyps starting at 9 months after tamoxifen treatment. scRNA-seq revealed aberrant stem cell-like characteristics of epithelial cells from polyp tissues of <i>Lkb1</i>^{<i>flox/+</i>};<i>Myh11-Cre/ERT2</i> mice. The Lkb1-associated polyps were further characterized by a branching smooth muscle core, abundant extracellular matrix deposition, and high immune cell infiltration. In addition, the Spp1–Cd44 or Spp1–Itga8/Itgb1 axes were identified as important interactions among epithelial, mesenchymal, and immune compartments in Lkb1-associated polyps. These characteristics of gastrointestinal polyps were also demonstrated in another mouse model, tamoxifen-inducible <i>Lkb1</i>^{<i>flox/flox</i>};<i>PDGFRα-Cre/ERT2</i> mice, which developed obvious gastrointestinal polyps as early as 2–3 months after tamoxifen treatment. Our findings further confirm the critical role of mesenchymal <i>Lkb1/Stk11</i> in gastrointestinal polyposis and provide novel insight into the cellular complexity of Lkb1-associated polyp biology. © 2024 The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"263 1","pages":"47-60"},"PeriodicalIF":7.3,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139929264","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":"TP53 disruptive mutation predicts platinum-based chemotherapy and PD-1/PD-L1 blockade response in urothelial carcinoma","authors":"Kaifeng Jin,&nbsp;Jingtong Xu,&nbsp;Xiaohe Su,&nbsp;Ziyue Xu,&nbsp;Bingyu Li,&nbsp;Ge Liu,&nbsp;Hailong Liu,&nbsp;Yiwei Wang,&nbsp;Yu Zhu,&nbsp;Le Xu,&nbsp;Weijuan Zhang,&nbsp;Zhaopei Liu,&nbsp;Zewei Wang,&nbsp;Yuan Chang,&nbsp;Jiejie Xu","doi":"10.1002/path.6266","DOIUrl":"10.1002/path.6266","url":null,"abstract":"<p><i>TP53</i> mutation is one of the most common genetic alterations in urothelial carcinoma (UrCa), and heterogeneity of <i>TP53</i> mutants leads to heterogeneous clinical outcomes. This study aimed to investigate the clinical relevance of specific <i>TP53</i> mutations in UrCa. In this study, a total of eight cohorts were enrolled, along with matched clinical annotation. <i>TP53</i> mutations were classified as disruptive and nondisruptive according to the degree of disturbance of p53 protein function and structure. We evaluated the clinical significance of <i>TP53</i> mutations in our local datasets and publicly available datasets. The co-occurring events of <i>TP53</i> mutations in UrCa, along with their therapeutic indications, functional effects, and the tumor immune microenvironment, were also investigated. <i>TP53</i> mutations were identified in 49.7% of the UrCa patients. Within this group, 25.1% of patients carried <i>TP53</i>^Disruptive mutations, a genetic alteration correlated with a significantly poorer overall survival (OS) when compared to individuals with <i>TP53</i>^{Nondisruptive} mutations and those with wild-type <i>TP53</i>. Significantly, patients with <i>TP53</i>^Disruptive mutations exhibit an increased probability of responding favorably to PD-1/PD-L1 blockade and chemoimmunotherapy. Meanwhile, there was no noteworthy distinction in OS among patients with varying <i>TP53</i> mutation status who underwent chemotherapy. Samples with <i>TP53</i>^Disruptive mutations showed an enriched APOBEC- and POLE-related mutational signature, as well as an elevated tumor mutation burden. The sensitivity to immunotherapy in tumors carrying <i>TP53</i>^Disruptive mutation may be attributed to the inflamed tumor microenvironment characterized by increased CD8⁺T cell infiltration and interferon-gamma signaling activation. In conclusion, UrCa patients with <i>TP53</i>^Disruptive mutations have shown reduced survival rates, yet they may respond well to PD-1/PD-L1 blockade therapy and chemoimmunotherapy. By distinguishing specific <i>TP53</i> mutations, we can improve risk stratification and offer personalized genomics-guided therapy to UrCa patients. © 2024 The Authors. <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":"263 2","pages":"139-149"},"PeriodicalIF":7.3,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139911704","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":"New analysis of atypical spermatocytic tumours reveals extensive heterogeneity and plasticity of germ cell tumours†","authors":"Ewa Rajpert-De Meyts,&nbsp;Anne Goriely,&nbsp;Kristian Almstrup","doi":"10.1002/path.6262","DOIUrl":"10.1002/path.6262","url":null,"abstract":"<p>Testicular germ cell tumours (TGCTs) derived from immature (type I) and pluripotent germ cell neoplasia <i>in situ</i> (GCNIS, type II) are characterised by remarkable phenotypic heterogeneity and plasticity. In contrast, the rare spermatocytic tumour (SpT, type III), derived from mature spermatogonia, is considered a homogenous and benign tumour but may occasionally present as an anaplastic or an aggressive sarcomatoid tumour. While various oncogenic processes had been proposed, the precise mechanism driving malignant progression remained elusive until the molecular characterisation of a series of atypical SpTs described in a recent issue of <i>The Journal of Pathology.</i> The emerging picture suggests the presence of two distinct trajectories for SpTs, involving either RAS/mitogen-activated protein kinase pathway mutations or a ploidy shift with secondary <i>TP53</i> mutations and/or gain of chromosome 12p, the latter known as pathognomonic for type II GCNIS-derived TGCTs. Here, we discuss the implications of these findings, seen from the perspective of germ cell biology and the unique features of different TGCTs. The evolving phenotype of SpTs, induced by genomic and epigenetic changes, illustrates that the concept of plasticity applies to all germ cell tumours, making them inherently heterogenous and capable of significant transformation during progression. © 2024 The Authors. <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":"263 1","pages":"1-4"},"PeriodicalIF":7.3,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6262","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139739997","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":"Integrated analyses of the genetic and clinicopathological features of cholangiolocarcinoma: cholangiolocarcinoma may be characterized by mismatch-repair deficiency","authors":"Kenta Makino,&nbsp;Takamichi Ishii,&nbsp;Haruhiko Takeda,&nbsp;Yoichi Saito,&nbsp;Yukio Fujiwara,&nbsp;Masakazu Fujimoto,&nbsp;Takashi Ito,&nbsp;Satoshi Wakama,&nbsp;Ken Kumagai,&nbsp;Fumiaki Munekage,&nbsp;Hiroshi Horie,&nbsp;Katsuhiro Tomofuji,&nbsp;Yu Oshima,&nbsp;Elena Yukie Uebayashi,&nbsp;Takayuki Kawai,&nbsp;Satoshi Ogiso,&nbsp;Ken Fukumitsu,&nbsp;Atsushi Takai,&nbsp;Hiroshi Seno,&nbsp;Etsuro Hatano","doi":"10.1002/path.6257","DOIUrl":"10.1002/path.6257","url":null,"abstract":"<p>Cholangiolocarcinoma (CLC) is a primary liver carcinoma that resembles the canals of Hering and that has been reported to be associated with stem cell features. Due to its rarity, the nature of CLC remains unclear, and its pathological classification remains controversial. To clarify the positioning of CLC in primary liver cancers and identify characteristics that could distinguish CLC from other liver cancers, we performed integrated analyses using whole-exome sequencing (WES), immunohistochemistry, and a retrospective review of clinical information on eight CLC cases and two cases of recurrent CLC. WES demonstrated that CLC includes <i>IDH1</i> and <i>BAP1</i> mutations, which are characteristic of intrahepatic cholangiocarcinoma (iCCA). A mutational signature analysis showed a pattern similar to that of iCCA, which was different from that of hepatocellular carcinoma (HCC). CLC cells, including CK7, CK19, and EpCAM, were positive for cholangiocytic differentiation markers. However, the hepatocytic differentiation marker AFP and stem cell marker SALL4 were completely negative. The immunostaining patterns of CLC with CD56 and epithelial membrane antigen were similar to those of the noncancerous bile ductules. In contrast, mutational signature cluster analyses revealed that CLC formed a cluster associated with mismatch-repair deficiency (dMMR), which was separate from iCCA. Therefore, to evaluate MMR status, we performed immunostaining of four MMR proteins (PMS2, MSH6, MLH1, and MSH2) and detected dMMR in almost all CLCs. In conclusion, CLC had highly similar characteristics to iCCA but not to HCC. CLC can be categorized as a subtype of iCCA. In contrast, CLC has characteristics of dMMR tumors that are not found in iCCA, suggesting that it should be treated distinctly from iCCA. © 2024 The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"263 1","pages":"32-46"},"PeriodicalIF":7.3,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139739996","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}