The Journal of Pathology最新文献

{"title":"Cell division-dependent dissemination following E-cadherin loss underlies initiation of diffuse-type gastric cancer","authors":"Jooske L Monster,&nbsp;Lars JS Kemp,&nbsp;Georg A Busslinger,&nbsp;Marjolein J Vliem,&nbsp;Lucca LM Derks,&nbsp;Annelot AL Staes,&nbsp;Tanya M Bisseling,&nbsp;Hans Clevers,&nbsp;Rachel S van der Post,&nbsp;Martijn Gloerich","doi":"10.1002/path.6277","DOIUrl":"10.1002/path.6277","url":null,"abstract":"<p>Loss of the cell–cell adhesion protein E-cadherin underlies the development of diffuse-type gastric cancer (DGC), which is characterized by the gradual accumulation of tumor cells originating from the gastric epithelium in the surrounding stroma. How E-cadherin deficiency drives DGC formation remains elusive. Therefore, we investigated the consequences of E-cadherin loss on gastric epithelial organization utilizing a human gastric organoid model and histological analyses of early-stage DGC lesions. E-cadherin depletion from gastric organoids recapitulates DGC initiation, with progressive loss of a single-layered architecture and detachment of individual cells. We found that E-cadherin deficiency in gastric epithelia does not lead to a general loss of epithelial cohesion but disrupts the spindle orientation machinery. This leads to a loss of planar cell division orientation and, consequently, daughter cells are positioned outside of the gastric epithelial layer. Although basally delaminated cells fail to detach and instead reintegrate into the epithelium, apically mispositioned daughter cells can trigger the gradual loss of the single-layered epithelial architecture. This impaired architecture hampers reintegration of mispositioned daughter cells and enables basally delaminated cells to disseminate into the surrounding matrix. Taken together, our findings describe how E-cadherin deficiency disrupts gastric epithelial architecture through displacement of dividing cells and provide new insights in the onset of DGC. © 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":"226-241"},"PeriodicalIF":7.3,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6277","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140593143","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":"Polyketide synthase positive Escherichia coli one-time measurement in stool is not informative of colorectal cancer risk in a screening setting","authors":"Willemijn de Klaver,&nbsp;Meike de Wit,&nbsp;Anne Bolijn,&nbsp;Marianne Tijssen,&nbsp;Pien Delis-van Diemen,&nbsp;Margriet Lemmens,&nbsp;Manon CW Spaander,&nbsp;Evelien Dekker,&nbsp;Monique E van Leerdam,&nbsp;Veerle MH Coupé,&nbsp;Ruben van Boxtel,&nbsp;Hans Clevers,&nbsp;Beatriz Carvalho,&nbsp;Gerrit A Meijer","doi":"10.1002/path.6276","DOIUrl":"10.1002/path.6276","url":null,"abstract":"<p>Environmental factors like the pathogenicity island <i>polyketide synthase positive (pks+) Escherichia coli</i> (<i>E. coli</i>) could have potential for risk stratification in colorectal cancer (CRC) screening. The association between <i>pks+ E. coli</i> measured in fecal immunochemical test (FIT) samples and the detection of advanced neoplasia (AN) at colonoscopy was investigated. Biobanked FIT samples were analyzed for both presence of <i>E. coli</i> and <i>pks+ E. coli</i> and correlated with colonoscopy findings; 5020 CRC screening participants were included. Controls were participants in which no relevant lesion was detected because of FIT-negative results (cut-off ≥15 μg Hb/g feces), a negative colonoscopy, or a colonoscopy during which only a nonadvanced polyp was detected. Cases were participants with AN [CRC, advanced adenoma (AA), or advanced serrated polyp (ASP)]. Existing DNA isolation and quantitative polymerase chain reaction (qPCR) procedures were used for the detection of <i>E. coli</i> and <i>pks+ E. coli</i> in stool. A total of 4542 (90.2%) individuals were <i>E. coli</i> positive, and 1322 (26.2%) were <i>pks+ E. coli</i> positive. The prevalence of <i>E. coli</i> in FIT samples from individuals with AN was 92.9% compared to 89.7% in FIT samples of controls (<i>p</i> = 0.010). The prevalence of <i>pks+ E. coli</i> in FIT samples from individuals with AN (28.6%) and controls (25.9%) was not significantly different (<i>p</i> = 0.13). The prevalences of <i>pks+ E. coli</i> in FIT samples from individuals with CRC, AA, or ASP were 29.6%, 28.3%, and 32.1%, respectively. In conclusion, the prevalence of <i>pks+ E. coli</i> in a screening population was 26.2% and did not differ significantly between individuals with AN and controls. These findings disqualify the straightforward option of using a snapshot measurement of <i>pks+ E. coli</i> in FIT samples as a stratification biomarker for CRC risk. © 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":"217-225"},"PeriodicalIF":7.3,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6276","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140317470","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":"Obliteration of portal venules contributes to portal hypertension in biliary cirrhosis","authors":"Shan Shan,&nbsp;Xinyan Zhao,&nbsp;Michelle A Wood-Trageser,&nbsp;Doudou Hu,&nbsp;Liwei Liu,&nbsp;Beining Qi,&nbsp;Jianbo Jian,&nbsp;Ping Wang,&nbsp;Wenjuan Lv,&nbsp;Chunhong Hu","doi":"10.1002/path.6273","DOIUrl":"10.1002/path.6273","url":null,"abstract":"<p>The effects of the obliteration of portal venules (OPV) in cirrhotic portal hypertension are poorly understood. To investigate its contribution to portal hypertension in biliary cirrhosis and its underlying mechanism, we evaluated OPV using two-dimensional (2D) histopathology in liver explants from patients with biliary atresia (BA, <i>n</i> = 63), primary biliary cholangitis (PBC, <i>n</i> = 18), and hepatitis B-related cirrhosis (Hep-B-cirrhosis, <i>n</i> = 35). Then, three-dimensional (3D) OPV was measured by X-ray phase-contrast CT in two parallel models in rats following bile duct ligation (BDL) or carbon tetrachloride (CCl₄) administration, representing biliary cirrhosis and post-necrotic cirrhosis, respectively. The portal pressure was also measured in the two models. Finally, the effects of proliferative bile ducts on OPV were investigated. We found that OPV was significantly more frequent in patients with biliary cirrhosis, including BA (78.57 ± 16.45%) and PBC (60.00 ± 17.15%), than that in Hep-B-cirrhotic patients (29.43 ± 14.94%, <i>p</i> &lt; 0.001). OPV occurred earlier, evidenced by the paired liver biopsy at a Kasai procedure (KP), and was irreversible even after a successful KP in the patients with BA. OPV was also significantly more frequent in the BDL models than in the CCl₄ models, as shown by 2D and 3D quantitative analysis. Portal pressure was significantly higher in the BDL model than that in the CCl₄ model. With the proliferation of bile ducts, portal venules were compressed and irreversibly occluded, contributing to the earlier and higher portal pressure in biliary cirrhosis. OPV, as a pre-sinusoidal component, plays a key role in the pathogenesis of portal hypertension in biliary cirrhosis. The proliferated bile ducts and ductules gradually take up the ‘territory’ originally attributed to portal venules and compress the portal venules, which may lead to OPV in biliary cirrhosis. © 2024 The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"263 2","pages":"178-189"},"PeriodicalIF":7.3,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140317469","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":"Research autopsy programmes in oncology: shared experience from 14 centres across the world","authors":"Tatjana Geukens,&nbsp;Marion Maetens,&nbsp;Jody E Hooper,&nbsp;Steffi Oesterreich,&nbsp;Adrian V Lee,&nbsp;Lori Miller,&nbsp;Jenny M Atkinson,&nbsp;Margaret Rosenzweig,&nbsp;Shannon Puhalla,&nbsp;Heather Thorne,&nbsp;Lisa Devereux,&nbsp;David Bowtell,&nbsp;Sherene Loi,&nbsp;Eliza R Bacon,&nbsp;Kena Ihle,&nbsp;Mihae Song,&nbsp;Lorna Rodriguez-Rodriguez,&nbsp;Alana L Welm,&nbsp;Lisa Gauchay,&nbsp;Rajmohan Murali,&nbsp;Pharto Chanda,&nbsp;Ali Karacay,&nbsp;Cristina Naceur-Lombardelli,&nbsp;Hayley Bridger,&nbsp;Charles Swanton,&nbsp;Mariam Jamal-Hanjani,&nbsp;Lori Kollath,&nbsp;Lawrence True,&nbsp;Colm Morrissey,&nbsp;Meagan Chambers,&nbsp;Arul M Chinnaiyan,&nbsp;Allecia Wilson,&nbsp;Rohit Mehra,&nbsp;Zachery Reichert,&nbsp;Lisa A Carey,&nbsp;Charles M Perou,&nbsp;Erin Kelly,&nbsp;Daichi Maeda,&nbsp;Akiteru Goto,&nbsp;Janina Kulka,&nbsp;Borbála Székely,&nbsp;A Marcell Szasz,&nbsp;Anna-Mária Tőkés,&nbsp;Wouter Van Den Bogaert,&nbsp;Giuseppe Floris,&nbsp;Christine Desmedt","doi":"10.1002/path.6271","DOIUrl":"10.1002/path.6271","url":null,"abstract":"<p>While there is a great clinical need to understand the biology of metastatic cancer in order to treat it more effectively, research is hampered by limited sample availability. Research autopsy programmes can crucially advance the field through synchronous, extensive, and high-volume sample collection. However, it remains an underused strategy in translational research. Via an extensive questionnaire, we collected information on the study design, enrolment strategy, study conduct, sample and data management, and challenges and opportunities of research autopsy programmes in oncology worldwide. Fourteen programmes participated in this study. Eight programmes operated 24 h/7 days, resulting in a lower median postmortem interval (time between death and start of the autopsy, 4 h) compared with those operating during working hours (9 h). Most programmes (<i>n</i> = 10) succeeded in collecting all samples within a median of 12 h after death. A large number of tumour sites were sampled during each autopsy (median 15.5 per patient). The median number of samples collected per patient was 58, including different processing methods for tumour samples but also non-tumour tissues and liquid biopsies. Unique biological insights derived from these samples included metastatic progression, treatment resistance, disease heterogeneity, tumour dormancy, interactions with the tumour micro-environment, and tumour representation in liquid biopsies. Tumour patient-derived xenograft (PDX) or organoid (PDO) models were additionally established, allowing for drug discovery and treatment sensitivity assays. Apart from the opportunities and achievements, we also present the challenges related with postmortem sample collections and strategies to overcome them, based on the shared experience of these 14 programmes. Through this work, we hope to increase the transparency of postmortem tissue donation, to encourage and aid the creation of new programmes, and to foster collaborations on these unique sample collections. © 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":"150-165"},"PeriodicalIF":7.3,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6271","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140317471","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":"UPK3A+ umbrella cell damage mediated by TLR3–NR2F6 triggers programmed destruction of urothelium in Hunner-type interstitial cystitis/painful bladder syndrome","authors":"Liao Peng,&nbsp;Jia-Wei Chen,&nbsp;Yuan-Zhuo Chen,&nbsp;Chi Zhang,&nbsp;Si-Hong Shen,&nbsp;Meng-Zhu Liu,&nbsp;Yang Fan,&nbsp;Shi-Qin Yang,&nbsp;Xiu-Zhen Zhang,&nbsp;Wei Wang,&nbsp;Xiao-Shuai Gao,&nbsp;Xing-Peng Di,&nbsp;Yu-Cheng Ma,&nbsp;Xiao Zeng,&nbsp;Hong Shen,&nbsp;Xi Jin,&nbsp;De-Yi Luo","doi":"10.1002/path.6275","DOIUrl":"10.1002/path.6275","url":null,"abstract":"<p>Urothelial damage and barrier dysfunction emerge as the foremost mechanisms in Hunner-type interstitial cystitis/bladder pain syndrome (HIC). Although treatments aimed at urothelial regeneration and repair have been employed, their therapeutic effectiveness remains limited due to the inadequate understanding of specific cell types involved in damage and the lack of specific molecular targets within these mechanisms. Therefore, we harnessed single-cell RNA sequencing to elucidate the heterogeneity and developmental trajectory of urothelial cells within HIC bladders. Through reclustering, we identified eight distinct clusters of urothelial cells. There was a significant reduction in UPK3A⁺ umbrella cells and a simultaneous increase in progenitor-like pluripotent cells (PPCs) within the HIC bladder. Pseudotime analysis of the urothelial cells in the HIC bladder revealed that cells faced challenges in differentiating into UPK3A⁺ umbrella cells, while PPCs exhibited substantial proliferation to compensate for the loss of UPK3A⁺ umbrella cells. The urothelium in HIC remains unrepaired, despite the substantial proliferation of PPCs. Thus, we propose that inhibiting the pivotal signaling pathways responsible for the injury to UPK3A⁺ umbrella cells is paramount for restoring the urothelial barrier and alleviating lower urinary tract symptoms in HIC patients. Subsequently, we identified key molecular pathways (TLR3 and NR2F6) associated with the injury of UPK3A⁺ umbrella cells in HIC urothelium. Finally, we conducted <i>in vitro</i> and <i>in vivo</i> experiments to confirm the potential of the TLR3–NR2F6 axis as a promising therapeutic target for HIC. These findings hold the potential to inhibit urothelial injury, providing promising clues for early diagnosis and functional bladder self-repair strategies for HIC patients. © 2024 The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"263 2","pages":"203-216"},"PeriodicalIF":7.3,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140317472","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":"Automated tumor immunophenotyping predicts clinical benefit from anti-PD-L1 immunotherapy","authors":"Xiao Li,&nbsp;Jeffrey Eastham,&nbsp;Jennifer M Giltnane,&nbsp;Wei Zou,&nbsp;Andries Zijlstra,&nbsp;Evgeniy Tabatsky,&nbsp;Romain Banchereau,&nbsp;Ching-Wei Chang,&nbsp;Barzin Y Nabet,&nbsp;Namrata S Patil,&nbsp;Luciana Molinero,&nbsp;Steve Chui,&nbsp;Maureen Harryman,&nbsp;Shari Lau,&nbsp;Linda Rangell,&nbsp;Yannick Waumans,&nbsp;Mark Kockx,&nbsp;Darya Orlova,&nbsp;Hartmut Koeppen","doi":"10.1002/path.6274","DOIUrl":"10.1002/path.6274","url":null,"abstract":"<p>Cancer immunotherapy has transformed the clinical approach to patients with malignancies, as profound benefits can be seen in a subset of patients. To identify this subset, biomarker analyses increasingly focus on phenotypic and functional evaluation of the tumor microenvironment to determine if density, spatial distribution, and cellular composition of immune cell infiltrates can provide prognostic and/or predictive information. Attempts have been made to develop standardized methods to evaluate immune infiltrates in the routine assessment of certain tumor types; however, broad adoption of this approach in clinical decision-making is still missing. We developed approaches to categorize solid tumors into ‘desert’, ‘excluded’, and ‘inflamed’ types according to the spatial distribution of CD8+ immune effector cells to determine the prognostic and/or predictive implications of such labels. To overcome the limitations of this subjective approach, we incrementally developed four automated analysis pipelines of increasing granularity and complexity for density and pattern assessment of immune effector cells. We show that categorization based on ‘manual’ observation is predictive for clinical benefit from anti-programmed death ligand 1 therapy in two large cohorts of patients with non-small cell lung cancer or triple-negative breast cancer. For the automated analysis we demonstrate that a combined approach outperforms individual pipelines and successfully relates spatial features to pathologist-based readouts and the patient's response to therapy. Our findings suggest that tumor immunophenotype generated by automated analysis pipelines should be evaluated further as potential predictive biomarkers for cancer immunotherapy. © 2024 The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"263 2","pages":"190-202"},"PeriodicalIF":7.3,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140205988","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 ‘Autophagy mediates survival of pancreatic tumour-initiating cells in a hypoxic microenvironment’","authors":"","doi":"10.1002/path.6281","DOIUrl":"10.1002/path.6281","url":null,"abstract":"<p>\u0000 <span>Vanessa Rausch</span>, <span>Li Liu</span>, <span>Anja Apel</span>, <span>Theresa Rettig</span>, <span>Jury Gladkich</span>, <span>Sabrina Labsch</span>, <span>Georgios Kallifatidis</span>, <span>Adam Kaczorowski</span>, <span>Ariane Groth</span>, <span>Wolfgang Gross</span>, <span>Martha M Gebhard</span>, <span>Peter Schemmer</span>, <span>Jens Werner</span>, <span>Alexei V Salnikov</span>, <span>Hanswalter Zentgraf</span>, <span>Markus W Büchler</span> and <span>Ingrid Herr</span>. <i>J Pathol</i> <span>2012</span>; <span>227</span><b>:</b> <span>325</span>–<span>335</span>. https://doi.org/10.1002/path.3994\u0000 </p><p>The corresponding author informed the editors of an error in Figure 2E of this article, first published on 19 January 2012 in Wiley Online Library (wileyonlinelibrary.com).</p><p>The authors apologize for their error and the inconvenience caused.</p><p>After examining their archive and discussing their findings with the editors and publisher, the author wished to make two additional changes:</p><p>These control β-actin bands were used also in the third row of Figure 4B, and this was scientifically valid.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"263 2","pages":"270"},"PeriodicalIF":7.3,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6281","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178850","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":"Patterns of structural variants within TP53 introns and relocation of the TP53 promoter: a commentary†","authors":"Hannah C Beird,&nbsp;Dimitri Lin,&nbsp;Alexander J Lazar,&nbsp;P Andrew Futreal","doi":"10.1002/path.6270","DOIUrl":"10.1002/path.6270","url":null,"abstract":"<p>Gene disruption from double-strand DNA breaks within introns is a mechanism of inactivating the tumor suppressor <i>TP53</i>. This occurs more frequently in osteosarcoma and biliary adenocarcinoma compared with other cancer types. The patterns of intron breakpoints within <i>TP53</i> do not correlate with prevalence, intron length, or overall genome-wide levels of rearrangements. Therefore, these breakpoints appear to be selected for reasons other than to disrupt <i>TP53</i>. A recent article published by Saba <i>et al</i> in <i>The Journal of Pathology</i> illustrates a benefit to having breakpoints within intron 1 using high-quality matched genomic and transcriptomic osteosarcoma sequencing data as well as <i>in vitro</i> validation. The authors describe how the rearrangement results in relocation of the <i>TP53</i> promoter region to regions upstream of genes that encode members of cartilage, growth plate development, osteoclast formation, and other <i>TP53</i>-related pathways. The upregulation of these genes by the <i>TP53</i> promoter are gain-of-function events that are likely to promote tumor development and growth. Therefore, this article presents a potential new paradigm in which a single mutation would result in both the loss of a tumor suppressor and the gain of an oncogenic program. © 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":"131-134"},"PeriodicalIF":7.3,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6270","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140118371","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":"Clonal analysis of metachronous double biliary tract cancers","authors":"Yuko Omori,&nbsp;Shuichi Aoki,&nbsp;Yusuke Ono,&nbsp;Takashi Kokumai,&nbsp;Shingo Yoshimachi,&nbsp;Hideaki Sato,&nbsp;Akiko Kusaka,&nbsp;Masahiro Iseki,&nbsp;Daisuke Douchi,&nbsp;Takayuki Miura,&nbsp;Shimpei Maeda,&nbsp;Masaharu Ishida,&nbsp;Masamichi Mizuma,&nbsp;Kei Nakagawa,&nbsp;Yusuke Mizukami,&nbsp;Toru Furukawa,&nbsp;Michiaki Unno","doi":"10.1002/path.6265","DOIUrl":"10.1002/path.6265","url":null,"abstract":"<p>The molecular mechanisms underpinning the development of metachronous tumors in the remnant bile duct following surgical resection of primary biliary tract carcinomas (BTCs) are unknown. This study aimed to elucidate these mechanisms by evaluating the clinicopathologic features of BTCs, the alterations to 31 BTC-related genes on targeted sequencing, and the aberrant expression of p53, p16, SMAD4, ARID1A and β-catenin on immunohistochemistry. Twelve consecutive patients who underwent resection of metachronous BTCs following primary BTC resection with negative bile duct margins were enrolled. Among the 12 metachronous tumors, six exhibited anterograde growth in the lower portion and six exhibited retrograde growth in the upper portion of the biliary tree. Surgical resection of metachronous BTCs resulted in recurrence-free survival in seven, local recurrence in five, and death in two patients. Nine achieved 5-year overall survival after primary surgery. Molecular analyses revealed that recurrently altered genes were: <i>TP53</i>, <i>SMAD4</i>, <i>CDKN2A</i>, <i>ELF3</i>, <i>ARID1A</i>, <i>GNAS</i>, <i>NF1</i>, <i>STK11</i>, <i>RNF43</i>, <i>KMT2D</i> and <i>ERBB3</i>. Each of these was altered in at least three cases. A comparison of the molecular features between 12 paired primary and metachronous BTCs indicated that 10 (83%) metachronous tumors developed in clonal association with corresponding primary tumors either successionally or phylogenically. The remaining two (17%) developed distinctly. The successional tumors consisted of direct or evolved primary tumor clones that spread along the bile duct. The phylogenic tumors consisted of genetically unstable clones and conferred a poor prognosis. Metachronous tumors distinct from their primaries harbored fewer mutations than successional and phylogenic tumors. In conclusion, over 80% of metachronous BTCs that develop following primary BTC resection are probably molecularly associated with their primaries in either a successional or a phylogenetic manner. Comparison between the molecular features of a metachronous tumor and those of a preceding tumor may provide effective therapeutic clues for the treatment of metachronous BTC. © 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":"113-127"},"PeriodicalIF":7.3,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6265","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140118370","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":"Correction to the ‘14th Joint Meeting of the BDIAP and The Pathological Society, Liverpool Pathology 2023, 27–29 June, 2023’ supplement","authors":"","doi":"10.1002/path.6267","DOIUrl":"10.1002/path.6267","url":null,"abstract":"<p>The Undergraduate Abstracts ‘The Contribution of Chloride Intracellular Channel 6 in Breast Cancer’ (Authors: <b>Ee J</b>, El-Toukhy S, Erkan B, Fakroun A, Ellis I, Rakha E, Green A), ‘Cathepsin V in the Pathogenesis of Luminal Breast Cancer: A Bimodal Approach’ (Authors: <b>Murray A</b>, Burden R, Sereesongsaeng N), ‘How Do We Encourage Student Awareness, Perception, and Interest in Pathology?’ (Author: <b>Williams G</b>) and ‘Accuracy of Intraoperative Frozen Section in the Assessment of Surgical Resection Margins in Penile Cancer’ (Authors: <b>Yunis M</b>, Pang K, Haider A, Freeman A, Hadway P, Nigam R, Rees R, Muneer A, Alnajjar H), have been omitted by error from the ‘14th Joint Meeting of the BDIAP and The Pathological Society, Liverpool Pathology 2023, 27–29 June, 2023’ supplement.</p><p>First Published 16 November 2023 in Wiley Online Library https://pathsocjournals.onlinelibrary.wiley.com/toc/10969896/2023/261/S1</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"263 1","pages":"128-130"},"PeriodicalIF":7.3,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140108676","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}