The Journal of Pathology最新文献

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Transcriptomic profiles of myxofibrosarcoma and undifferentiated pleomorphic sarcoma correlate with clinical and genomic features 肌纤维肉瘤和未分化多形性肉瘤的转录组特征与临床和基因组特征的关系
IF 5.6 2区 医学
The Journal of Pathology Pub Date : 2024-09-11 DOI: 10.1002/path.6347
Shamik Mitra, Akanksha Farswan, Paul Piccinelli, Saskia Sydow, Asle Hesla, Panagiotis Tsagkozis, Fredrik Vult von Steyern, Martin Almqvist, Mikael Eriksson, Linda Magnusson, Jenny Nilsson, Nischalan Pillay, Fredrik Mertens
{"title":"Transcriptomic profiles of myxofibrosarcoma and undifferentiated pleomorphic sarcoma correlate with clinical and genomic features","authors":"Shamik Mitra,&nbsp;Akanksha Farswan,&nbsp;Paul Piccinelli,&nbsp;Saskia Sydow,&nbsp;Asle Hesla,&nbsp;Panagiotis Tsagkozis,&nbsp;Fredrik Vult von Steyern,&nbsp;Martin Almqvist,&nbsp;Mikael Eriksson,&nbsp;Linda Magnusson,&nbsp;Jenny Nilsson,&nbsp;Nischalan Pillay,&nbsp;Fredrik Mertens","doi":"10.1002/path.6347","DOIUrl":"10.1002/path.6347","url":null,"abstract":"<p>Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are two common and aggressive subtypes of soft tissue sarcoma. The aim of this study was to assess potential transcriptomic differences between MFS and UPS tumours and to evaluate the extent to which differences in gene expression profiles were associated with genomic and clinical features. The study included 162 patients with tumours diagnosed as MFS (<i>N</i> = 62) or UPS (<i>N</i> = 100). The patients had been diagnosed and treated at two Swedish sarcoma centres during a 30-year period. For gene expression profiling and gene fusion detection all tumours were analysed using RNA-sequencing and could be compared with data on clinical outcome (<i>N</i> = 155), global copy number profiles (<i>N</i> = 145), and gene mutations (<i>N</i> = 128). Gene expression profiling revealed three transcriptomic clusters (TCs) without any clear separation of MFS and UPS. One TC was associated with longer metastasis-free survival. These tumours had lower tumour mutation burden (TMB), were enriched for a copy number signature representative of focal LOH and chromosomal instability on a diploid background, and were relatively immune-depleted. MFS and UPS showed extensive genomic overlap, with whole genome doubling occurring more frequently among the latter. The results support the idea that MFS and UPS tumours have largely overlapping genomic and transcriptomic features, with UPS tumours showing more aggressive behaviour and more complex genomes. Independently of the tumour type, clinically relevant subgroups were revealed by gene expression analysis, and the finding of multiple genomic subgroups strongly suggest the existence of subgroups of relevance to treatment stratification. © 2024 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":"264 3","pages":"293-304"},"PeriodicalIF":5.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6347","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142190673","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}
引用次数: 0
Common progenitor origin for Rosai–Dorfman disease and clear cell sarcoma 罗赛-多夫曼病和透明细胞肉瘤的共同祖细胞起源。
IF 5.6 2区 医学
The Journal of Pathology Pub Date : 2024-09-03 DOI: 10.1002/path.6345
Aki Sato, Nozomi Yusa, Hiroyuki Takamori, Eigo Shimizu, Kazuaki Yokoyama, Satoshi Ichikawa, Hisayuki Yokoyama, Yuki Kasahara, Kodai Enda, Fumiyoshi Fujishima, Ryo Ichinohasama, Yasunori Ota, Seiya Imoto, Yasuhito Nannya
{"title":"Common progenitor origin for Rosai–Dorfman disease and clear cell sarcoma","authors":"Aki Sato,&nbsp;Nozomi Yusa,&nbsp;Hiroyuki Takamori,&nbsp;Eigo Shimizu,&nbsp;Kazuaki Yokoyama,&nbsp;Satoshi Ichikawa,&nbsp;Hisayuki Yokoyama,&nbsp;Yuki Kasahara,&nbsp;Kodai Enda,&nbsp;Fumiyoshi Fujishima,&nbsp;Ryo Ichinohasama,&nbsp;Yasunori Ota,&nbsp;Seiya Imoto,&nbsp;Yasuhito Nannya","doi":"10.1002/path.6345","DOIUrl":"10.1002/path.6345","url":null,"abstract":"<p>Histiocytic neoplasms (HNs) in adults have been reported to be associated with a high prevalence of coexisting haematological and solid malignancies. While a proportion of coexisting HNs and haematological malignancies share identical genetic alterations, the genetic association between HNs and solid malignancies has scarcely been reported. We report a case of Rosai–Dorfman disease (RDD) complicated by coexisting clear cell sarcoma (CCS). RDD is a rare HN. CCS is an ultrarare soft tissue sarcoma with a poor prognosis. Mutation analysis with whole-exome sequencing revealed six shared somatic alterations including <i>NRAS</i> p.G12S and <i>TP53</i> c.559+1G&gt;A in both the RDD and CCS tissue. This is the first evidence of a clonal relationship between RDD and solid malignancies using mutational analysis. We hypothesise that neural crest cells, which originate in CCS, are likely the common cells of origin for RDD and CCS. This case helps to unravel the underlying clinicopathological mechanisms of increased association of solid malignancies in HNs. © 2024 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":"264 3","pages":"243-249"},"PeriodicalIF":5.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6345","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118600","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}
引用次数: 0
Single-cell transcriptomics identifies aberrant glomerular angiogenic signalling in the early stages of WT1 kidney disease 单细胞转录组学发现 WT1 肾病早期肾小球血管生成信号异常。
IF 5.6 2区 医学
The Journal of Pathology Pub Date : 2024-08-23 DOI: 10.1002/path.6339
Jennifer C Chandler, Daniyal J Jafree, Saif Malik, Gideon Pomeranz, Mary Ball, Maria Kolatsi-Joannou, Alice Piapi, William J Mason, Andrew V Benest, David O Bates, Aleksandra Letunovska, Reem Al-Saadi, Marion Rabant, Olivia Boyer, Kathy Pritchard-Jones, Paul J Winyard, Andrew S Mason, Adrian S Woolf, Aoife M Waters, David A Long
{"title":"Single-cell transcriptomics identifies aberrant glomerular angiogenic signalling in the early stages of WT1 kidney disease","authors":"Jennifer C Chandler,&nbsp;Daniyal J Jafree,&nbsp;Saif Malik,&nbsp;Gideon Pomeranz,&nbsp;Mary Ball,&nbsp;Maria Kolatsi-Joannou,&nbsp;Alice Piapi,&nbsp;William J Mason,&nbsp;Andrew V Benest,&nbsp;David O Bates,&nbsp;Aleksandra Letunovska,&nbsp;Reem Al-Saadi,&nbsp;Marion Rabant,&nbsp;Olivia Boyer,&nbsp;Kathy Pritchard-Jones,&nbsp;Paul J Winyard,&nbsp;Andrew S Mason,&nbsp;Adrian S Woolf,&nbsp;Aoife M Waters,&nbsp;David A Long","doi":"10.1002/path.6339","DOIUrl":"10.1002/path.6339","url":null,"abstract":"<p><i>WT1</i> encodes a podocyte transcription factor whose variants can cause an untreatable glomerular disease in early childhood. Although WT1 regulates many podocyte genes, it is poorly understood which of them are initiators in disease and how they subsequently influence other cell-types in the glomerulus. We hypothesised that this could be resolved using single-cell RNA sequencing (scRNA-seq) and ligand-receptor analysis to profile glomerular cell–cell communication during the early stages of disease in mice harbouring an orthologous human mutation in WT1 (<i>Wt1</i><sup><i>R394W/+</i></sup>). Podocytes were the most dysregulated cell-type in the early stages of <i>Wt1</i><sup><i>R394W/+</i></sup> disease, with disrupted angiogenic signalling between podocytes and the endothelium, including the significant downregulation of transcripts for the vascular factors Vegfa and Nrp1. These signalling changes preceded glomerular endothelial cell loss in advancing disease, a feature also observed in biopsy samples from human WT1 glomerulopathies. Addition of conditioned medium from murine <i>Wt1</i><sup><i>R394W/+</i></sup> primary podocytes to wild-type glomerular endothelial cells resulted in impaired endothelial looping and reduced vascular complexity. Despite the loss of key angiogenic molecules in <i>Wt1</i><sup><i>R394W/+</i></sup> podocytes, the pro-vascular molecule adrenomedullin was upregulated in <i>Wt1</i><sup><i>R394W/+</i></sup> podocytes and plasma and its further administration was able to rescue the impaired looping observed when glomerular endothelium was exposed to <i>Wt1</i><sup><i>R394W/+</i></sup> podocyte medium. In comparative analyses, adrenomedullin upregulation was part of a common injury signature across multiple murine and human glomerular disease datasets, whilst other gene changes were unique to WT1 disease. Collectively, our study describes a novel role for altered angiogenic signalling in the initiation of WT1 glomerulopathy. We also identify adrenomedullin as a proangiogenic factor, which despite being upregulated in early injury, offers an insufficient protective response due to the wider milieu of dampened vascular signalling that results in endothelial cell loss in later disease. © 2024 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":"264 2","pages":"212-227"},"PeriodicalIF":5.6,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6339","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034679","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}
引用次数: 0
Single-cell transcriptomic analysis reveals that the APP–CD74 axis promotes immunosuppression and progression of testicular tumors 单细胞转录组分析显示,APP-CD74 轴促进了免疫抑制和睾丸肿瘤的进展。
IF 5.6 2区 医学
The Journal of Pathology Pub Date : 2024-08-19 DOI: 10.1002/path.6343
Guo Chen, Wei Wang, Xin Wei, Yulin Chen, Liao Peng, Rui Qu, Yi Luo, Shengyin He, Yugao Liu, Jie Du, Ran Lu, Siying Li, Chuangwen Fan, Sujun Chen, Yi Dai, Luo Yang
{"title":"Single-cell transcriptomic analysis reveals that the APP–CD74 axis promotes immunosuppression and progression of testicular tumors","authors":"Guo Chen,&nbsp;Wei Wang,&nbsp;Xin Wei,&nbsp;Yulin Chen,&nbsp;Liao Peng,&nbsp;Rui Qu,&nbsp;Yi Luo,&nbsp;Shengyin He,&nbsp;Yugao Liu,&nbsp;Jie Du,&nbsp;Ran Lu,&nbsp;Siying Li,&nbsp;Chuangwen Fan,&nbsp;Sujun Chen,&nbsp;Yi Dai,&nbsp;Luo Yang","doi":"10.1002/path.6343","DOIUrl":"10.1002/path.6343","url":null,"abstract":"<p>Testicular tumors represent the most common malignancy among young men. Nevertheless, the pathogenesis and molecular underpinning of testicular tumors remain largely elusive. We aimed to delineate the intricate intra-tumoral heterogeneity and the network of intercellular communication within the tumor microenvironment. A total of 40,760 single-cell transcriptomes were analyzed, encompassing samples from six individuals with seminomas, two patients with mixed germ cell tumors, one patient with a Leydig cell tumor, and three healthy donors. Five distinct malignant subclusters were identified in the constructed landscape. Among them, malignant 1 and 3 subclusters were associated with a more immunosuppressive state and displayed worse disease-free survival. Further analysis identified that APP–CD74 interactions were significantly strengthened between malignant 1 and 3 subclusters and 14 types of immune subpopulations. In addition, we established an aberrant spermatogenesis trajectory and delineated the global gene alterations of somatic cells in seminoma testes. Sertoli cells were identified as the somatic cell type that differed the most from healthy donors to seminoma testes. Cellular communication between spermatogonial stem cells and Sertoli cells is disturbed in seminoma testes. Our study delineates the intra-tumoral heterogeneity and the tumor immune microenvironment in testicular tumors, offering novel insights for targeted therapy. © 2024 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":"264 3","pages":"250-269"},"PeriodicalIF":5.6,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6343","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003239","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}
引用次数: 0
The unique metabolome of clear cell ovarian carcinoma 透明细胞卵巢癌的独特代谢组。
IF 5.6 2区 医学
The Journal of Pathology Pub Date : 2024-08-03 DOI: 10.1002/path.6329
Jennifer X Ji, Lien N Hoang, Dawn R Cochrane, Amy Lum, Janine Senz, David Farnell, Basile Tessier-Cloutier, David G Huntsman, Ramon I Klein Geltink
{"title":"The unique metabolome of clear cell ovarian carcinoma","authors":"Jennifer X Ji,&nbsp;Lien N Hoang,&nbsp;Dawn R Cochrane,&nbsp;Amy Lum,&nbsp;Janine Senz,&nbsp;David Farnell,&nbsp;Basile Tessier-Cloutier,&nbsp;David G Huntsman,&nbsp;Ramon I Klein Geltink","doi":"10.1002/path.6329","DOIUrl":"10.1002/path.6329","url":null,"abstract":"<p>Clear cell ovarian carcinoma (CCOC) is an aggressive malignancy affecting younger women. Despite ovarian cancer subtypes having diverse molecular and clinical characteristics, the mainstay of treatment for advanced stage disease remains cytotoxic chemotherapy. Late stage CCOC is resistant to conventional chemotherapy, which means a suboptimal outcome for patients affected. Despite detailed genomic, epigenomic, transcriptomic, and proteomic characterisation, subtype-specific treatment for CCOC has shown little progress. The unique glycogen accumulation defining CCOC suggests altered metabolic pathway activity and dependency. This study presents the first metabolomic landscape of ovarian cancer subtypes, including 42 CCOC, 20 high-grade serous and 21 endometrioid ovarian carcinomas, together comprising the three most common ovarian carcinoma subtypes. We describe a distinct metabolomic landscape of CCOC compared with other ovarian cancer subtypes, including alterations in energy utilisation and cysteine metabolism. In addition, we identify CCOC-specific alterations in metabolic pathways including serine biosynthesis and ROS-associated pathways that could serve as potential therapeutic targets. Our study provides the first in-depth study into the metabolome of ovarian cancers and a rich resource to support ongoing research efforts to identify subtype-specific therapeutic targets that could improve the dismal outcome for patients with this devastating malignancy. © 2024 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":"264 2","pages":"160-173"},"PeriodicalIF":5.6,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6329","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877963","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}
引用次数: 0
NMRK2 is an efficient diagnostic indicator for Xp11.2 translocation renal cell carcinoma NMRK2 是 Xp11.2 易位肾细胞癌的有效诊断指标。
IF 5.6 2区 医学
The Journal of Pathology Pub Date : 2024-08-02 DOI: 10.1002/path.6340
Huayi Feng, Shouqing Cao, Shihui Fu, Junxiao Liu, Yu Gao, Zhouhuan Dong, Tianwei Cai, Lequan Wen, Zhuang Xiong, Shangwei Li, Xu Zhang, Xin Ma, Xiubin Li
{"title":"NMRK2 is an efficient diagnostic indicator for Xp11.2 translocation renal cell carcinoma","authors":"Huayi Feng,&nbsp;Shouqing Cao,&nbsp;Shihui Fu,&nbsp;Junxiao Liu,&nbsp;Yu Gao,&nbsp;Zhouhuan Dong,&nbsp;Tianwei Cai,&nbsp;Lequan Wen,&nbsp;Zhuang Xiong,&nbsp;Shangwei Li,&nbsp;Xu Zhang,&nbsp;Xin Ma,&nbsp;Xiubin Li","doi":"10.1002/path.6340","DOIUrl":"10.1002/path.6340","url":null,"abstract":"<p>Xp11.2 translocation renal cell carcinomas (tRCC) are a rare and highly malignant type of renal cancer, lacking efficient diagnostic indicators and therapeutic targets. Through the analysis of public databases and our cohort, we identified NMRK2 as a potential diagnostic marker for distinguishing Xp11.2 tRCC from kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) due to its specific upregulation in Xp11.2 tRCC tissues. Mechanistically, we discovered that TFE3 fusion protein binds to the promoter of the NMRK2 gene, leading to its upregulation. Importantly, we established RNA- and protein-based diagnostic methods for identifying Xp11.2 tRCC based on NMRK2 expression levels, and the diagnostic performance of our methods was comparable to a dual-color break-apart fluorescence <i>in situ</i> hybridization assay. Moreover, we successfully identified fresh Xp11.2 tRCC tissues after surgical excision using our diagnostic methods and established an immortalized Xp11.2 tRCC cell line for further research purposes. Functional studies revealed that NMRK2 promotes the progression of Xp11.2 tRCC by upregulating the NAD<sup>+</sup>/NADH ratio, and supplementation with β-nicotinamide mononucleotide (NMN) or nicotinamide riboside chloride (NR), effectively rescued the phenotypes induced by the knockdown of NMRK2 in Xp11.2 tRCC. Taken together, these data introduce a new diagnostic indicator capable of accurately distinguishing Xp11.2 tRCC and highlight the possibility of developing novel targeted therapeutics. © 2024 The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"264 2","pages":"228-240"},"PeriodicalIF":5.6,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873757","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}
引用次数: 0
Spatial effects of infiltrating T cells on neighbouring cancer cells and prognosis in stage III CRC patients 浸润 T 细胞对邻近癌细胞的空间影响与 III 期 CRC 患者的预后。
IF 5.6 2区 医学
The Journal of Pathology Pub Date : 2024-08-02 DOI: 10.1002/path.6327
Mohammadreza Azimi, Sanghee Cho, Emir Bozkurt, Elizabeth McDonough, Batuhan Kisakol, Anna Matveeva, Manuela Salvucci, Heiko Dussmann, Simon McDade, Canan Firat, Nil Urganci, Jinru Shia, Daniel B Longley, Fiona Ginty, Jochen HM Prehn
{"title":"Spatial effects of infiltrating T cells on neighbouring cancer cells and prognosis in stage III CRC patients","authors":"Mohammadreza Azimi,&nbsp;Sanghee Cho,&nbsp;Emir Bozkurt,&nbsp;Elizabeth McDonough,&nbsp;Batuhan Kisakol,&nbsp;Anna Matveeva,&nbsp;Manuela Salvucci,&nbsp;Heiko Dussmann,&nbsp;Simon McDade,&nbsp;Canan Firat,&nbsp;Nil Urganci,&nbsp;Jinru Shia,&nbsp;Daniel B Longley,&nbsp;Fiona Ginty,&nbsp;Jochen HM Prehn","doi":"10.1002/path.6327","DOIUrl":"10.1002/path.6327","url":null,"abstract":"<p>Colorectal cancer (CRC) is one of the most frequently occurring cancers, but prognostic biomarkers identifying patients at risk of recurrence are still lacking. In this study, we aimed to investigate in more detail the spatial relationship between intratumoural T cells, cancer cells, and cancer cell hallmarks as prognostic biomarkers in stage III colorectal cancer patients. We conducted multiplexed imaging of 56 protein markers at single-cell resolution on resected fixed tissue from stage III CRC patients who received adjuvant 5-fluorouracil (5FU)-based chemotherapy. Images underwent segmentation for tumour, stroma, and immune cells, and cancer cell ‘state’ protein marker expression was quantified at a cellular level. We developed a Python package for estimation of spatial proximity, nearest neighbour analysis focusing on cancer cell–T-cell interactions at single-cell level. In our discovery cohort (Memorial Sloan Kettering samples), we processed 462 core samples (total number of cells: 1,669,228) from 221 adjuvant 5FU-treated stage III patients. The validation cohort (Huntsville Clearview Cancer Center samples) consisted of 272 samples (total number of cells: 853,398) from 98 stage III CRC patients. While there were trends for an association between the percentage of cytotoxic T cells (across the whole cancer core), it did not reach significance (discovery cohort: <i>p</i> = 0.07; validation cohort: <i>p</i> = 0.19). We next utilised our region-based nearest neighbour approach to determine the spatial relationships between cytotoxic T cells, helper T cells, and cancer cell clusters. In both cohorts, we found that shorter distance between cytotoxic T cells, T helper cells, and cancer cells was significantly associated with increased disease-free survival. An unsupervised trained model that clustered patients based on the median distance between immune cells and cancer cells, as well as protein expression profiles, successfully classified patients into low-risk and high-risk groups (discovery cohort: <i>p</i> = 0.01; validation cohort: <i>p</i> = 0.003). © 2024 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":"264 2","pages":"148-159"},"PeriodicalIF":5.6,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6327","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873758","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}
引用次数: 0
Changes in the tumour microenvironment mark the transition from serous borderline tumour to low-grade serous carcinoma 肿瘤微环境的变化标志着从浆液性边界肿瘤向低级别浆液性癌的过渡。
IF 5.6 2区 医学
The Journal of Pathology Pub Date : 2024-07-31 DOI: 10.1002/path.6338
Rodrigo Vallejos, Almira Zhantuyakova, Gian Luca Negri, Spencer D Martin, Sandra E Spencer, Shelby Thornton, Samuel Leung, Branden Lynch, Yimei Qin, Christine Chow, Brooke Liang, Sabrina Zdravko, J Maxwell Douglas, Katy Milne, Bridget Mateyko, Brad H Nelson, Brooke E Howitt, Felix KF Kommoss, Lars-Christian Horn, Lien Hoang, Naveena Singh, Gregg B Morin, David G Huntsman, Dawn Cochrane
{"title":"Changes in the tumour microenvironment mark the transition from serous borderline tumour to low-grade serous carcinoma","authors":"Rodrigo Vallejos,&nbsp;Almira Zhantuyakova,&nbsp;Gian Luca Negri,&nbsp;Spencer D Martin,&nbsp;Sandra E Spencer,&nbsp;Shelby Thornton,&nbsp;Samuel Leung,&nbsp;Branden Lynch,&nbsp;Yimei Qin,&nbsp;Christine Chow,&nbsp;Brooke Liang,&nbsp;Sabrina Zdravko,&nbsp;J Maxwell Douglas,&nbsp;Katy Milne,&nbsp;Bridget Mateyko,&nbsp;Brad H Nelson,&nbsp;Brooke E Howitt,&nbsp;Felix KF Kommoss,&nbsp;Lars-Christian Horn,&nbsp;Lien Hoang,&nbsp;Naveena Singh,&nbsp;Gregg B Morin,&nbsp;David G Huntsman,&nbsp;Dawn Cochrane","doi":"10.1002/path.6338","DOIUrl":"10.1002/path.6338","url":null,"abstract":"<p>Low-grade serous ovarian carcinoma (LGSC) is a rare and lethal subtype of ovarian cancer. LGSC is pathologically, biologically, and clinically distinct from the more common high-grade serous ovarian carcinoma (HGSC). LGSC arises from serous borderline ovarian tumours (SBTs). The mechanism of transformation for SBTs to LGSC remains poorly understood. To better understand the biology of LGSC, we performed whole proteome profiling of formalin-fixed, paraffin-embedded tissue blocks of LGSC (<i>n</i> = 11), HGSC (<i>n</i> = 19), and SBTs (<i>n</i> = 26). We identified that the whole proteome is able to distinguish between histotypes of the ovarian epithelial tumours. Proteins associated with the tumour microenvironment were differentially expressed between LGSC and SBTs. Fibroblast activation protein (FAP), a protein expressed in cancer-associated fibroblasts, is the most differentially abundant protein in LGSC compared with SBT. Multiplex immunohistochemistry (IHC) for immune markers (CD20, CD79a, CD3, CD8, and CD68) was performed to determine the presence of B cells, T cells, and macrophages. The LGSC FAP<sup>+</sup> stroma was associated with greater abundance of Tregs and M2 macrophages, features not present in SBTs. Our proteomics cohort reveals that there are changes in the tumour microenvironment in LGSC compared with its putative precursor lesion, SBT. These changes suggest that the tumour microenvironment provides a supportive environment for LGSC tumourigenesis and progression. Thus, targeting the tumour microenvironment of LGSC may be a viable therapeutic strategy. © 2024 The Pathological Society of Great Britain and Ireland.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"264 2","pages":"197-211"},"PeriodicalIF":5.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854369","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}
引用次数: 0
Correction to ‘Quantitative proteomics identifies altered O-GlcNAcylation of structural, synaptic and memory-associated proteins in Alzheimer's disease’ 定量蛋白质组学发现阿尔茨海默病中结构蛋白、突触蛋白和记忆相关蛋白的 O-GlcNAcylation 发生了改变 "一文的更正。
IF 5.6 2区 医学
The Journal of Pathology Pub Date : 2024-07-30 DOI: 10.1002/path.6342
{"title":"Correction to ‘Quantitative proteomics identifies altered O-GlcNAcylation of structural, synaptic and memory-associated proteins in Alzheimer's disease’","authors":"","doi":"10.1002/path.6342","DOIUrl":"10.1002/path.6342","url":null,"abstract":"<p>Sheng Wang, Feng Yang, Vladislav A Petyuk, Anil K Shukla, Matthew E Monroe, Marina A Gritsenko, Karin D Rodland, Richard D Smith, Wei-Jun Qian, Cheng-Xin Gong and Tao Liu. <i>J Pathol</i> 2017; <b>243:</b> 78–88. https://doi.org/10.1002/path.4929</p><p>Tao Liu, one of the co-corresponding authors, has informed the editors of an error in supplementary material, Figure S1 of this article, first published on 28 June 2017 in Wiley Online Library (https://onlinelibrary.wiley.com/).</p><p>Cheng-Xin Gong, the other co-corresponding author, agrees with this correction, and both apologise for the error and the inconvenience caused.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"264 2","pages":"241"},"PeriodicalIF":5.6,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6342","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791526","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}
引用次数: 0
Pan-cancer evaluation of tumor-infiltrating lymphocytes and programmed cell death protein ligand-1 in metastatic biopsies and matched primary tumors 对转移性活检组织和匹配的原发肿瘤中的肿瘤浸润淋巴细胞和程序性细胞死亡蛋白配体-1进行泛癌评估。
IF 5.6 2区 医学
The Journal of Pathology Pub Date : 2024-07-29 DOI: 10.1002/path.6334
Zakhia El Beaino, Célia Dupain, Grégoire Marret, Xavier Paoletti, Laëtitia Fuhrmann, Charlotte Martinat, Yves Allory, Maral Halladjian, Ivan Bièche, Christophe Le Tourneau, Maud Kamal, Anne Vincent-Salomon
{"title":"Pan-cancer evaluation of tumor-infiltrating lymphocytes and programmed cell death protein ligand-1 in metastatic biopsies and matched primary tumors","authors":"Zakhia El Beaino,&nbsp;Célia Dupain,&nbsp;Grégoire Marret,&nbsp;Xavier Paoletti,&nbsp;Laëtitia Fuhrmann,&nbsp;Charlotte Martinat,&nbsp;Yves Allory,&nbsp;Maral Halladjian,&nbsp;Ivan Bièche,&nbsp;Christophe Le Tourneau,&nbsp;Maud Kamal,&nbsp;Anne Vincent-Salomon","doi":"10.1002/path.6334","DOIUrl":"10.1002/path.6334","url":null,"abstract":"<p>Tumor immunological characterization includes evaluation of tumor-infiltrating lymphocytes (TILs) and programmed cell death protein ligand-1 (PD-L1) expression. This study investigated TIL distribution, its prognostic value, and PD-L1 expression in metastatic and matched primary tumors (PTs). Specimens from 550 pan-cancer patients of the SHIVA01 trial (NCT01771458) with available metastatic biopsy and 111 matched PTs were evaluated for TILs and PD-L1. Combined positive score (CPS), tumor proportion score (TPS), and immune cell (IC) score were determined. TILs and PD-L1 were assessed according to PT organ of origin, histological subtype, and metastatic biopsy site. We found that TIL distribution in metastases did not vary according to PT organ of origin, histological subtype, or metastatic biopsy site, with a median of 10% (range: 0–70). TILs were decreased in metastases compared to PT (20% [5–60] versus 10% [0–40], <i>p</i> &lt; 0.0001). CPS varied according to histological subtype (<i>p</i> = 0.02) and biopsy site (<i>p</i> &lt; 0.02). TPS varied according to PT organ of origin (<i>p</i> = 0.003), histological subtype (<i>p</i> = 0.0004), and metastatic biopsy site (<i>p</i> = 0.00004). TPS was higher in metastases than in PT (<i>p</i> &lt; 0.0001). TILs in metastases did not correlate with overall survival. In conclusion, metastases harbored fewer TILs than matched PT, regardless of PT organ of origin, histological subtype, and metastatic biopsy site. PD-L1 expression increased with disease progression. © 2024 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":"264 2","pages":"186-196"},"PeriodicalIF":5.6,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6334","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141786697","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}
引用次数: 0
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