-
Patterns of structural variants within TP53 introns and relocation of the TP53 promoter: a commentary† J. Pathol. (IF 7.3) Pub Date : 2024-03-14 Hannah C Beird, Dimitri Lin, Alexander J Lazar, P Andrew Futreal
Gene disruption from double‐strand DNA breaks within introns is a mechanism of inactivating the tumor suppressor TP53. This occurs more frequently in osteosarcoma and biliary adenocarcinoma compared with other cancer types. The patterns of intron breakpoints within TP53 do not correlate with prevalence, intron length, or overall genome‐wide levels of rearrangements. Therefore, these breakpoints appear
-
Clonal analysis of metachronous double biliary tract cancers J. Pathol. (IF 7.3) Pub Date : 2024-03-14 Yuko Omori, Shuichi Aoki, Yusuke Ono, Takashi Kokumai, Shingo Yoshimachi, Hideaki Sato, Akiko Kusaka, Masahiro Iseki, Daisuke Douchi, Takayuki Miura, Shimpei Maeda, Masaharu Ishida, Masamichi Mizuma, Kei Nakagawa, Yusuke Mizukami, Toru Furukawa, Michiaki Unno
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
-
Correction to the ‘14th Joint Meeting of the BDIAP and The Pathological Society, Liverpool Pathology 2023, 27–29 June, 2023’ supplement J. Pathol. (IF 7.3) Pub Date : 2024-03-13
The Undergraduate Abstracts ‘The Contribution of Chloride Intracellular Channel 6 in Breast Cancer’ (Authors: Ee J, 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: Murray A, Burden R, Sereesongsaeng N), ‘How Do We Encourage Student Awareness, Perception, and Interest in Pathology?’ (Author: Williams
-
-
List of Reviewers J. Pathol. (IF 7.3) Pub Date : 2024-03-05
The high quality of manuscripts published in The Journal of Pathology largely relies on the standards set by our expert reviewers. The Journal of Pathology 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).
-
AI‐guided histopathology predicts brain metastasis in lung cancer patients J. Pathol. (IF 7.3) Pub Date : 2024-03-04 Haowen Zhou, Mark Watson, Cory T Bernadt, Steven (Siyu) Lin, Chieh‐yu Lin, Jon H Ritter, Alexander Wein, Simon Mahler, Sid Rawal, Ramaswamy Govindan, Changhuei Yang, Richard J Cote
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&E‐stained primary tumor tissue sections from stage I–III NSCLC patients
-
Serine/threonine‐protein kinase D2‐mediated phosphorylation of DSG2 threonine 730 promotes esophageal squamous cell carcinoma progression J. Pathol. (IF 7.3) Pub Date : 2024-02-27 Yin‐Qiao Liu, Yi‐Wei Xu, Zheng‐Tan Zheng, Die Li, Chao‐Qun Hong, Hao‐Qiang Dai, Jun‐Hao Wang, Ling‐Yu Chu, Lian‐Di Liao, Hai‐Ying Zou, En‐Min Li, Jian‐Jun Xie, Wang‐Kai Fang
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
-
KAT8/SIRT7‐mediated Fascin‐K41 acetylation/deacetylation regulates tumor metastasis in esophageal squamous cell carcinoma J. Pathol. (IF 7.3) Pub Date : 2024-02-27 Da‐Jia Li, Yin‐Wei Cheng, Jin‐Mei Pan, Zhen‐Chang Guo, Shao‐Hong Wang, Qing‐Feng Huang, Ping‐Juan Nie, Wen‐Qi Shi, Xiu‐E Xu, Bing Wen, Jin‐Ling Zhong, Zhi‐Da Zhang, Zhi‐Yong Wu, Hui Zhao, Lian‐Di Liao, Jian‐Yi Wu, Kai Zhang, Geng Dong, En‐Min Li, Li‐Yan Xu
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
-
Hourglass, a compass navigating global and regional heterogeneity of pancreatic cancer† J. Pathol. (IF 7.3) Pub Date : 2024-02-26 Derya Bakırdöğen, Kıvanç Görgülü, Hana Algül
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
-
Cellular and molecular characteristics of stromal Lkb1 deficiency‐induced gastrointestinal polyposis based on single‐cell RNA sequencing J. Pathol. (IF 7.3) Pub Date : 2024-02-23 Zhaohua Cai, Yangjing Jiang, Huan Tong, Min Liang, Yijie Huang, Liang Fang, Feng Liang, Yunwen Hu, Xin Shi, Jian Wang, Zi Wang, Qingqi Ji, Huanhuan Huo, Linghong Shen, Ben He
Liver kinase B1 (Lkb1), encoded by serine/threonine kinase (Stk11), 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
-
TP53 disruptive mutation predicts platinum‐based chemotherapy and PD‐1/PD‐L1 blockade response in urothelial carcinoma J. Pathol. (IF 7.3) Pub Date : 2024-02-21 Kaifeng Jin, Jingtong Xu, Xiaohe Su, Ziyue Xu, Bingyu Li, Ge Liu, Hailong Liu, Yiwei Wang, Yu Zhu, Le Xu, Weijuan Zhang, Zhaopei Liu, Zewei Wang, Yuan Chang, Jiejie Xu
TP53 mutation is one of the most common genetic alterations in urothelial carcinoma (UrCa), and heterogeneity of TP53 mutants leads to heterogeneous clinical outcomes. This study aimed to investigate the clinical relevance of specific TP53 mutations in UrCa. In this study, a total of eight cohorts were enrolled, along with matched clinical annotation. TP53 mutations were classified as disruptive and
-
New analysis of atypical spermatocytic tumours reveals extensive heterogeneity and plasticity of germ cell tumours† J. Pathol. (IF 7.3) Pub Date : 2024-02-16 Ewa Rajpert-De Meyts, Anne Goriely, Kristian Almstrup
Testicular germ cell tumours (TGCTs) derived from immature (type I) and pluripotent germ cell neoplasia in situ (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
-
Integrated analyses of the genetic and clinicopathological features of cholangiolocarcinoma: cholangiolocarcinoma may be characterized by mismatch-repair deficiency J. Pathol. (IF 7.3) Pub Date : 2024-02-16 Kenta Makino, Takamichi Ishii, Haruhiko Takeda, Yoichi Saito, Yukio Fujiwara, Masakazu Fujimoto, Takashi Ito, Satoshi Wakama, Ken Kumagai, Fumiaki Munekage, Hiroshi Horie, Katsuhiro Tomofuji, Yu Oshima, Elena Yukie Uebayashi, Takayuki Kawai, Satoshi Ogiso, Ken Fukumitsu, Atsushi Takai, Hiroshi Seno, Etsuro Hatano
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
-
The spatial landscape of T cells in the microenvironment of stage III lung adenocarcinoma J. Pathol. (IF 7.3) Pub Date : 2024-02-16 Ziqing Zeng, Weijiao Du, Fan Yang, Zhenzhen Hui, Yunliang Wang, Peng Zhang, Xiying Zhang, Wenwen Yu, Xiubao Ren, Feng Wei
This study aimed to provide more information for prognostic stratification for patients through an analysis of the T-cell spatial landscape. It involved analyzing stained tissue sections of 80 patients with stage III lung adenocarcinoma (LUAD) using multiplex immunofluorescence and exploring the spatial landscape of T cells and their relationship with prognosis in the center of the tumor (CT) and invasive
-
Comprehensive clinicopathological, molecular, and methylation analysis of mesenchymal tumors with NTRK and other kinase gene aberrations J. Pathol. (IF 7.3) Pub Date : 2024-02-09 Natálie Klubíčková, Josephine K Dermawan, Elaheh Mosaieby, Petr Martínek, Tomáš Vaněček, Veronika Hájková, Nikola Ptáková, Petr Grossmann, Petr Šteiner, Marián Švajdler, Zdeněk Kinkor, Květoslava Michalová, Peter Szepe, Lukáš Plank, Stanislava Hederová, Alexandra Kolenová, Neofit Juriev Spasov, Kemal Kosemehmetoglu, Leo Pažanin, Zuzana Špůrková, Martin Baník, Luděk Baumruk, Anders Meyer, Antonina Kalmykova
Alterations in kinase genes such as NTRK1/2/3, RET, and BRAF underlie infantile fibrosarcoma (IFS), the emerging entity ‘NTRK-rearranged spindle cell neoplasms’ included in the latest WHO classification, and a growing set of tumors with overlapping clinical and pathological features. In this study, we conducted a comprehensive clinicopathological and molecular analysis of 22 cases of IFS and other
-
Defect in degradation of glycogenin-exposed residual glycogen in lysosomes is the fundamental pathomechanism of Pompe disease J. Pathol. (IF 7.3) Pub Date : 2024-02-09 Na Zhang, Fuchen Liu, Yuying Zhao, Xiaohan Sun, Bing Wen, Jian-qiang Lu, Chuanzhu Yan, Duoling Li
Pompe disease is a lysosomal storage disorder that preferentially affects muscles, and it is caused by GAA mutation coding acid alpha-glucosidase in lysosome and glycophagy deficiency. While the initial pathology of Pompe disease is glycogen accumulation in lysosomes, the special role of the lysosomal pathway in glycogen degradation is not fully understood. Hence, we investigated the characteristics
-
Gene therapy with AAV9-SGPL1 in an animal model of lung fibrosis J. Pathol. (IF 7.3) Pub Date : 2024-02-09 Aritra Bhattacharyya, Ranjha Khan, Joanna Y Lee, Gizachew Tassew, Babak Oskouian, Maria L Allende, Richard L Proia, Xiaoyang Yin, Javier G Ortega, Mallar Bhattacharya, Julie D Saba
Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease of the lung that leads rapidly to respiratory failure. Novel approaches to treatment are urgently needed. The bioactive lipid sphingosine-1-phosphate (S1P) is increased in IPF lungs and promotes proinflammatory and profibrotic TGF-β signaling. Hence, decreasing lung S1P represents a potential therapeutic strategy for IPF. S1P is
-
Upcycling HOXB13: enhancing prostate cancer detection with a novel antibody† J. Pathol. (IF 7.3) Pub Date : 2024-02-09 Anke Augspach, Mark A Rubin
Prostate cancer is one of the most prevalent and, upon metastasis, deadliest cancers in men. Timely identification is essential for effective treatment. Furthermore, accurate determination of prostatic origin is crucial for personalized therapy once the cancer has spread. However, current prostate cancer screening methods are lacking. A recent article in The Journal of Pathology addresses this issue
-
Comprehensive splicing analysis of the alternatively spliced CHEK2 exons 8 and 10 reveals three enhancer/silencer-rich regions and 38 spliceogenic variants J. Pathol. (IF 7.3) Pub Date : 2024-02-09 Lara Sanoguera-Miralles, Inés Llinares-Burguet, Elena Bueno-Martínez, Lobna Ramadane-Morchadi, Cristiana Stuani, Alberto Valenzuela-Palomo, Alicia García-Álvarez, Pedro Pérez-Segura, Emanuele Buratti, Miguel de la Hoya, Eladio A Velasco-Sampedro
Splicing is controlled by a large set of regulatory elements (SREs) including splicing enhancers and silencers, which are involved in exon recognition. Variants at these motifs may dysregulate splicing and trigger loss-of-function transcripts associated with disease. Our goal here was to study the alternatively spliced exons 8 and 10 of the breast cancer susceptibility gene CHEK2. For this purpose
-
Detailed DNA methylation characterisation of phyllodes tumours identifies a signature of malignancy and distinguishes phyllodes from metaplastic breast carcinoma J. Pathol. (IF 7.3) Pub Date : 2024-02-01 Braydon Meyer, Clare Stirzaker, Sonny Ramkomuth, Kate Harvey, Belinda Chan, Cheok Soon Lee, Rooshdiya Karim, Niantao Deng, Kelly A Avery-Kiejda, Rodney J Scott, Sunil Lakhani, Stephen Fox, Elizabeth Robbins, Joo-Shik Shin, Jane Beith, Anthony Gill, Loretta Sioson, Charles Chan, Mrudula Krishnaswamy, Caroline Cooper, Sanjay Warrier, Cindy Mak, John EJ Rasko, Charles G Bailey, Alexander Swarbrick, Susan
Phyllodes tumours (PTs) are rare fibroepithelial lesions of the breast that are classified as benign, borderline, or malignant. As little is known about the molecular underpinnings of PTs, current diagnosis relies on histological examination. However, accurate classification is often difficult, particularly for distinguishing borderline from malignant PTs. Furthermore, PTs can be misdiagnosed as other
-
Chemokine profiling of melanoma–macrophage crosstalk identifies CCL8 and CCL15 as prognostic factors in cutaneous melanoma J. Pathol. (IF 7.3) Pub Date : 2024-01-30 Celia Barrio-Alonso, Alicia Nieto-Valle, Elena García-Martínez, Alba Gutiérrez-Seijo, Verónica Parra-Blanco, Iván Márquez-Rodas, José Antonio Avilés-Izquierdo, Paloma Sánchez-Mateos, Rafael Samaniego
During cancer evolution, tumor cells attract and dynamically interact with monocytes/macrophages. To find biomarkers of disease progression in human melanoma, we used unbiased RNA sequencing and secretome analyses of tumor–macrophage co-cultures. Pathway analysis of genes differentially modulated in human macrophages exposed to melanoma cells revealed a general upregulation of inflammatory hallmark
-
A partial epithelial-mesenchymal transition signature for highly aggressive colorectal cancer cells that survive under nutrient restriction J. Pathol. (IF 7.3) Pub Date : 2024-01-18 Gil A Pastorino, Ilir Sheraj, Kerstin Huebner, Giulio Ferrero, Philipp Kunze, Arndt Hartmann, Chuanpit Hampel, Hepsen Hazal Husnugil, Arnatchai Maiuthed, Florian Gebhart, Fynn Schlattmann, Aliye Ezgi Gulec Taskiran, Goksu Oral, Ralph Palmisano, Barbara Pardini, Alessio Naccarati, Katharina Erlenbach-Wuensch, Sreeparna Banerjee, Regine Schneider-Stock
Partial epithelial-mesenchymal transition (p-EMT) has recently been identified as a hybrid state consisting of cells with both epithelial and mesenchymal characteristics and is associated with the migration, metastasis, and chemoresistance of cancer cells. Here, we describe the induction of p-EMT in starved colorectal cancer (CRC) cells and identify a p-EMT gene signature that can predict prognosis
-
Spatial profiling reveals tissue-specific neuro-immune interactions in gastroenteropancreatic neuroendocrine tumors J. Pathol. (IF 7.3) Pub Date : 2024-01-17 Suzann Duan, Travis W Sawyer, Brandon L Witten, Heyu Song, Tobias Else, Juanita L Merchant
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous malignancies that arise from complex cellular interactions within the tissue microenvironment. Here, we sought to decipher tumor-derived signals from the surrounding microenvironment by applying digital spatial profiling (DSP) to hormone-secreting and non-functional GEP-NETs. By combining this approach with in vitro studies of
-
Image-based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno-oncology Biomarker Working Group on Breast Cancer J. Pathol. (IF 7.3) Pub Date : 2024-01-17 Chowdhury Arif Jahangir, David B Page, Glenn Broeckx, Claudia A Gonzalez, Caoimbhe Burke, Clodagh Murphy, Jorge S Reis-Filho, Amy Ly, Paul W Harms, Rajarsi R Gupta, Michael Vieth, Akira I Hida, Mohamed Kahila, Zuzana Kos, Paul J van Diest, Sara Verbandt, Jeppe Thagaard, Reena Khiroya, Khalid Abduljabbar, Gabriela Acosta Haab, Balazs Acs, Sylvia Adams, Jonas S Almeida, Isabel Alvarado-Cabrero, Farid
Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers
-
FANCD2 deficiency sensitizes SHH medulloblastoma to radiotherapy via ferroptosis J. Pathol. (IF 7.3) Pub Date : 2024-01-17 Hong Zhou, Yan-Xia Wang, Min Wu, Xi Lan, Dongfang Xiang, Ruili Cai, Qinghua Ma, Jingya Miao, Xuanyu Fang, Junjie Wang, Dan Luo, Zhicheng He, Youhong Cui, Ping Liang, Yan Wang, Xiu-Wu Bian
Radiotherapy is one of the standard therapeutic regimens for medulloblastoma (MB). Tumor cells utilize DNA damage repair (DDR) mechanisms to survive and develop resistance during radiotherapy. It has been found that targeting DDR sensitizes tumor cells to radiotherapy in several types of cancer, but whether and how DDR pathways are involved in the MB radiotherapy response remain to be determined. Single-cell
-
Dichotomous role of the serine/threonine kinase MAP4K4 in pancreatic ductal adenocarcinoma onset and metastasis through control of AKT and ERK pathways J. Pathol. (IF 7.3) Pub Date : 2024-01-17 Amelie Juin, Heather J Spence, Laura M Machesky
MAP4K4 is a serine/threonine kinase of the STE20 family involved in the regulation of actin cytoskeleton dynamics and cell motility. It has been proposed as a target of angiogenesis and inhibitors show potential in cardioprotection. MAP4K4 also mediates cell invasion in vitro, is overexpressed in various types of cancer, and is associated with poor patient prognosis. Recently, MAP4K4 has been shown
-
Jeremy Jass Prize for Research Excellence in Pathology 2022 J. Pathol. (IF 7.3) Pub Date : 2024-01-09
Every year the Editorial team of The Journal of Pathology awards the Jeremy Jass Prize for Research Excellence to the paper published in the prior calendar year that they perceive to be of the highest scientific calibre. Selection is always difficult because the standard of papers published in the Journal is so high. The following paper was selected for the Jass Prize for the calendar year 2022: Peter
-
TRPM2-dependent autophagy inhibition exacerbates oxidative stress-induced CXCL16 secretion by keratinocytes in vitiligo J. Pathol. (IF 7.3) Pub Date : 2024-01-08 Pan Kang, Yinghan Wang, Jianru Chen, Yuqian Chang, Weigang Zhang, Tingting Cui, Xiuli Yi, Shuli Li, Chunying Li
Vitiligo is a depigmented skin disease due to the destruction of melanocytes. Under oxidative stress, keratinocyte-derived chemokine C-X-C motif ligand 16 (CXCL16) plays a critical role in recruiting CD8+ T cells, which kill melanocytes. Autophagy serves as a protective cell survival mechanism and impairment of autophagy has been linked to increased secretion of the proinflammatory cytokines. However
-
PAX2 is regulated by estrogen/progesterone through promoter methylation in endometrioid adenocarcinoma and has an important role in carcinogenesis via the AKT/mTOR signaling pathway J. Pathol. (IF 7.3) Pub Date : 2024-01-07 Hui Chen, Lingjun Li, Huimin Liu, Ping Qin, Ruichao Chen, Shaoyan Liu, Hanzhen Xiong, Yang Li, Zhongfeng Yang, Mingyu Xie, Haili Yang, Qingping Jiang
Endometrioid adenocarcinoma (EEC) is one of the most common cancers of the female reproductive system. In recent years, much emphasis has been placed on early diagnosis and treatment. PAX2 (Paired box 2) inactivation is reportedly an important biomarker for endometrioid intraepithelial neoplasia (EIN) and EEC. However, the role of PAX2 in EEC carcinogenesis remains unclear. PAX2 expression and associated
-
Mutational signature and prognosis in adenocarcinoma of the bladder J. Pathol. (IF 7.3) Pub Date : 2024-01-05 Guoliang Yang, Akezhouli Shahatiaili, Shihao Bai, Liyang Wang, Di Jin, Ming Cao, Peipei Su, Qiang Liu, Kun Tao, Qi Long, Yi Shi, Jing Xiao, Futong Tian, Lianhua Zhang, Haige Chen, Xianbin Su
Adenocarcinoma of the bladder is a rare urinary bladder carcinoma with limited therapy options due to lack of molecular characterization. Here, we aimed to reveal the mutational and transcriptomic landscapes of adenocarcinoma of the bladder and assess any relationship with prognosis. Between February 2015 and June 2021, a total of 23 patients with adenocarcinoma of the bladder were enrolled. These
-
Neural stem cell homeostasis is affected in cortical organoids carrying a mutation in Angiogenin J. Pathol. (IF 7.3) Pub Date : 2024-01-05 Ross Ferguson, Michael A van Es, Leonard H van den Berg, Vasanta Subramanian
Mutations in Angiogenin (ANG) and TARDBP encoding the 43 kDa transactive response DNA binding protein (TDP-43) are associated with amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). ANG is neuroprotective and plays a role in stem cell dynamics in the haematopoietic system. We obtained skin fibroblasts from members of an ALS-FTD family, one with mutation in ANG, one with mutation in
-
The fifth edition of the WHO classification of mature B-cell neoplasms: open questions for research J. Pathol. (IF 7.3) Pub Date : 2024-01-05 Sarah E Coupland, Ming-Qing Du, Judith A Ferry, Daphne de Jong, Joseph D Khoury, Lorenzo Leoncini, Kikkeri N Naresh, German Ott, Reiner Siebert, Luc Xerri
The fifth edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5) is the product of an evidence-based evolution of the revised fourth edition with wide multidisciplinary consultation. Nonetheless, while every classification incorporates scientific advances and aims to improve upon the prior version, medical knowledge remains incomplete and individual neoplasms
-
Integrated transcriptomic landscape of the effect of anti-steatotic treatments in high-fat diet mouse models of non-alcoholic fatty liver disease J. Pathol. (IF 7.3) Pub Date : 2024-01-05 Isabel Fuster-Martínez, José F Català-Senent, Marta R Hidalgo, Francisco J Roig, Juan V Esplugues, Nadezda Apostolova, Francisco García-García, Ana Blas-García
High-fat diet (HFD) mouse models are widely used in research to develop medications to treat non-alcoholic fatty liver disease (NAFLD), as they mimic the steatosis, inflammation, and hepatic fibrosis typically found in this complex human disease. The aims of this study were to identify a complete transcriptomic signature of these mouse models and to characterize the transcriptional impact exerted by
-
Relapses in early-stage follicular lymphoma frequently develop via a divergent evolution from their clonally related precursor cells J. Pathol. (IF 7.3) Pub Date : 2023-12-29 Jasmine Makker, Andrew Wotherspoon, Maria-Myrsini Tzioni, Zi Chen, Sarah Guo, Dan Jiang, Calogero Casa, Francesco Cucco, Ming-Qing Du
Follicular lymphoma (FL) develops through a stepwise acquisition of cooperative genetic changes with t(14;18)(q32;q21)/IGH::BCL2 occurring early at the pre-B stage of B-cell development. Patients with FL typically show an indolent clinical course, remitting and relapsing with the eventual development of resistance to treatments. Interestingly, the majority of transformed FL do not progress directly
-
Ramipril therapy in integrin α1-null, autosomal recessive Alport mice triples lifespan: mechanistic clues from RNA-seq analysis J. Pathol. (IF 7.3) Pub Date : 2023-12-21 Jacob Madison, Kevin Wilhelm, Daniel T Meehan, Michael Anne Gratton, Denise Vosik, Gina Samuelson, Megan Ott, John Fascianella, Noa Nelson, Dominic Cosgrove
The standard of care for patients with Alport syndrome (AS) is angiotensin-converting enzyme (ACE) inhibitors. In autosomal recessive Alport (ARAS) mice, ACE inhibitors double lifespan. We previously showed that deletion of Itga1 in Alport mice [double-knockout (DKO) mice] increased lifespan by 50%. This effect seemed dependent on the prevention of laminin 211-mediated podocyte injury. Here, we treated
-
Downregulated BMP–Smad1/5/8 signaling causes emphysema via dysfunction of alveolar type II epithelial cells J. Pathol. (IF 7.3) Pub Date : 2023-12-18 Xi Zheng, Xiaoying Chen, Xiaoxiao Hu, Lidan Chen, Nana Mi, Qianqian Zhong, Linfang Wang, Chensheng Lin, YiPing Chen, Fancai Lai, Xuefeng Hu, Yanding Zhang
Bone morphogenetic protein (BMP)–Smad1/5/8 signaling plays a crucial regulatory role in lung development and adult lung homeostasis. However, it remains elusive whether BMP–Smad1/5/8 signaling is involved in the pathogenesis of emphysema. In this study, we downregulated BMP–Smad1/5/8 signaling by overexpressing its antagonist Noggin in adult mouse alveolar type II epithelial cells (AT2s), resulting
-
Extracting structured information from unstructured histopathology reports using generative pre-trained transformer 4 (GPT-4) J. Pathol. (IF 7.3) Pub Date : 2023-12-14 Daniel Truhn, Chiara ML Loeffler, Gustav Müller-Franzes, Sven Nebelung, Katherine J Hewitt, Sebastian Brandner, Keno K Bressem, Sebastian Foersch, Jakob Nikolas Kather
Deep learning applied to whole-slide histopathology images (WSIs) has the potential to enhance precision oncology and alleviate the workload of experts. However, developing these models necessitates large amounts of data with ground truth labels, which can be both time-consuming and expensive to obtain. Pathology reports are typically unstructured or poorly structured texts, and efforts to implement
-
List of Reviewers J. Pathol. (IF 7.3) Pub Date : 2023-12-06
The high quality of manuscripts published in The Journal of Pathology largely relies on the standards set by our expert reviewers. The Journal of Pathology wishes to thank the following 458 individuals who assisted by reviewing articles for the Journal in 2022 (affiliations shown are those currently held in our system).
-
CD8+ T cells in fetal membranes display a unique phenotype, and their activation is involved in the pathophysiology of spontaneous preterm birth J. Pathol. (IF 7.3) Pub Date : 2023-11-29 Yinan Jiang, Xintong Lai, Yuxu Liu, Cheng Yang, Zhicui Liu, Xiaorui Liu, Tiantian Yu, Cailian Chen, Asma Khanniche, Jianxia Fan, Yi Lin, Weihong Zeng
Preterm labor/birth is the leading cause of perinatal mortality and morbidity worldwide. Previous studies demonstrated that T cells were crucial for maintaining maternal–fetal immune tolerance during the first trimester of pregnancy; however, their phenotypes and functions in labor and delivery remain largely unknown. We recruited three cohorts of women at delivery for T-cell immunophenotyping in the
-
Disruption of the TP53 locus in osteosarcoma leads to TP53 promoter gene fusions and restoration of parts of the TP53 signalling pathway J. Pathol. (IF 7.3) Pub Date : 2023-11-27 Karim H Saba, Valeria Difilippo, Michal Kovac, Louise Cornmark, Linda Magnusson, Jenny Nilsson, Hilda van den Bos, Diana CJ Spierings, Mahtab Bidgoli, Tord Jonson, Vaiyapuri P Sumathi, Otte Brosjö, Johan Staaf, Floris Foijer, Emelie Styring, Michaela Nathrath, Daniel Baumhoer, Karolin H Nord
TP53 is the most frequently mutated gene in human cancer. This gene shows not only loss-of-function mutations but also recurrent missense mutations with gain-of-function activity. We have studied the primary bone malignancy osteosarcoma, which harbours one of the most rearranged genomes of all cancers. This is odd since it primarily affects children and adolescents who have not lived the long life
-
Decreased HER2 expression in endometrial cancer following anti-HER2 therapy J. Pathol. (IF 7.3) Pub Date : 2023-11-27 M Herman Chui, David N Brown, Arnaud Da Cruz Paula, Edaise M da Silva, Amir Momeni-Boroujeni, Jorge S Reis-Filho, Yanming Zhang, Vicky Makker, Lora Hedrick Ellenson, Britta Weigelt
Trastuzumab has demonstrated clinical efficacy in the treatment of HER2-positive serous endometrial cancer (EC), which led to its incorporation into standard-of-care management of this aggressive disease. Acquired resistance remains an important challenge, however, and its underlying mechanisms in EC are unknown. To define the molecular changes that occur in response to anti-HER2 therapy in EC, targeted
-
Single-cell RNA sequencing of human prostate basal epithelial cells reveals zone-specific cellular populations and gene expression signatures J. Pathol. (IF 7.3) Pub Date : 2023-11-20 Jordan E Vellky, Yaqi Wu, Daniel Moline, Jenny Drnevich, Mark Maienschein-Cline, Klara Valyi-Nagy, Andre Kajdacsy-Balla, Donald J Vander Griend
Despite evidence of genetic signatures in normal tissue correlating with disease risk, prospectively identifying genetic drivers and cell types that underlie subsequent pathologies has historically been challenging. The human prostate is an ideal model to investigate this phenomenon because it is anatomically segregated into three glandular zones (central, peripheral, and transition) that develop differential
-
Genetic and immune landscape evolution in MMR-deficient colorectal cancer J. Pathol. (IF 7.3) Pub Date : 2023-11-15 Benjamin R Challoner, Andrew Woolston, David Lau, Marta Buzzetti, Caroline Fong, Louise J Barber, Gayathri Anandappa, Richard Crux, Ioannis Assiotis, Kerry Fenwick, Ruwaida Begum, Dipa Begum, Tom Lund, Nanna Sivamanoharan, Harold B Sansano, Melissa Domingo-Arada, Amina Tran, Hardev Pandha, David Church, Bryony Eccles, Richard Ellis, Stephen Falk, Mark Hill, Daniel Krell, Nirupa Murugaesu, Luke Nolan
Mismatch repair-deficient (MMRd) colorectal cancers (CRCs) have high mutation burdens, which make these tumours immunogenic and many respond to immune checkpoint inhibitors. The MMRd hypermutator phenotype may also promote intratumour heterogeneity (ITH) and cancer evolution. We applied multiregion sequencing and CD8 and programmed death ligand 1 (PD-L1) immunostaining to systematically investigate
-
Deficiency of inflammation-sensing protein neuropilin-2 in myeloid-derived macrophages exacerbates colitis via NF-κB activation J. Pathol. (IF 7.3) Pub Date : 2023-11-10 Tong Li, Jingjing Ran, Zhiyong Miao, Min Yang, Dachao Mou, Yunhan Jiang, Xiaoqiu Xu, Qibing Xie, Ke Jin
Neuropilin-2 (NRP2) is a multifunctional protein engaged in the regulation of angiogenesis, lymphangiogenesis, axon guidance, and tumor metastasis, but its function in colitis remains unclear. Here, we found that NRP2 was an inflammation-sensing protein rapidly and dramatically induced in myeloid cells, especially in macrophages, under inflammatory contexts. NRP2 deficiency in myeloid cells exacerbated
-
Mechanisms of carboplatin- and paclitaxel-dependent induction of premature senescence and pro-cancerogenic conversion of normal peritoneal mesothelium and fibroblasts J. Pathol. (IF 7.3) Pub Date : 2023-11-09 Szymon Rutecki, Martyna Pakuła-Iwańska, Agnieszka Leśniewska-Bocianowska, Julia Matuszewska, Daniel Rychlewski, Paweł Uruski, Łukasz Stryczyński, Eryk Naumowicz, Sebastian Szubert, Andrzej Tykarski, Justyna Mikuła-Pietrasik, Krzysztof Książek
Carboplatin (CPT) and paclitaxel (PCT) are the optimal non-surgical treatment of epithelial ovarian cancer (EOC). Although their growth-restricting influence on EOC cells is well known, their impact on normal peritoneal cells, including mesothelium (PMCs) and fibroblasts (PFBs), is poorly understood. Here, we investigated whether, and if so, by what mechanism, CPT and PCT induce senescence of omental
-
CD27/CD70 pathway activation in primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder J. Pathol. (IF 7.3) Pub Date : 2023-11-07 Julia Richter, Ilske Oschlies, Katharina Kock, Thomas Wüseke, Jochen Haag, Karoline Koch, Wolfram Klapper
Primary cutaneous CD4+ small or medium T-cell lymphoproliferative disorder (PCSM-LPD) is a clonal T-cell proliferation disease confined to the skin. PCSM-LPD shares expression of T follicular helper (Tfh) cell markers with various mature T-cell lymphomas. However, the benign presentation of PCSM-LPD contrasts the clinical behavior of other Tfh-lymphomas. The aim of our study was to delineate the molecular
-
New risk factors and molecular landscapes of hepatic angiosarcoma in the Taiwanese population† J. Pathol. (IF 7.3) Pub Date : 2023-11-06 Felicia Chung, Jiri Zavadil
Hepatic angiosarcoma is a rare, highly aggressive malignancy of the liver. The tumorigenesis of hepatic angiosarcoma has been relatively understudied in terms of aetiology and molecular properties. A recent study published in The Journal of Pathology revealed a strong association between hepatic angiosarcoma incidence and chronic kidney disease, particularly in end-stage renal disease using population-based
-
Opposing roles for ADAMTS2 and ADAMTS14 in myofibroblast differentiation and function J. Pathol. (IF 7.3) Pub Date : 2023-11-06 Edward P Carter, Kubra K Yoneten, Nuria Gavara, Eleanor J Tyler, Valentine Gauthier, Elizabeth R Murray, Peter ten Dijke, Angus J Cameron, Oliver Pearce, Richard P Grose
Crosstalk between cancer and stellate cells is pivotal in pancreatic cancer, resulting in differentiation of stellate cells into myofibroblasts that drives tumour progression. To assess cooperative mechanisms in a 3D context, we generated chimeric spheroids using human and mouse cancer and stellate cells. Species-specific deconvolution of bulk-RNA sequencing data revealed cell type-specific transcriptomes
-
Bullous pemphigoid induced by IgG targeting type XVII collagen non-NC16A/NC15A extracellular domains is driven by Fc gamma receptor- and complement-mediated effector mechanisms and is ameliorated by neonatal Fc receptor blockade J. Pathol. (IF 7.3) Pub Date : 2023-11-06 Manuela Pigors, Sabrina Patzelt, Niklas Reichhelm, Jenny Dworschak, Stanislav Khil'chenko, Shirin Emtenani, Katja Bieber, Maxi Hofrichter, Mayumi Kamaguchi, Stephanie Goletz, Gabriele Köhl, Jörg Köhl, Lars Komorowski, Christian Probst, Katrien Vanderheyden, Bianca Balbino, Ralf J Ludwig, Peter Verheesen, Enno Schmidt
Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by autoantibodies targeting type XVII collagen (Col17) with the noncollagenous 16A (NC16A) ectodomain representing the immunodominant site. The role of additional extracellular targets of Col17 outside NC16A has not been unequivocally demonstrated. In this study, we showed that Col17 ectodomain-reactive patient sera depleted
-
Liverpool Pathology 2023. 14th Joint Meeting of the BDIAP and The Pathological Society, 27-29 June 2023. J. Pathol. (IF 7.3) Pub Date : 2023-11-01
-
Characterization of HOXB13 expression patterns in localized and metastatic castration-resistant prostate cancer J. Pathol. (IF 7.3) Pub Date : 2023-10-18 Radhika A Patel, Erolcan Sayar, Ilsa Coleman, Martine P Roudier, Brian Hanratty, Jin-Yih Low, Neha Jaiswal, Azra Ajkunic, Ruth Dumpit, Caner Ercan, Nina Salama, Valerie P O'Brien, William B Isaacs, Jonathan I Epstein, Angelo M De Marzo, Bruce J Trock, Jun Luo, W Nathaniel Brennen, Maria Tretiakova, Funda Vakar-Lopez, Lawrence D True, David W Goodrich, Eva Corey, Colm Morrissey, Peter S Nelson, Paula
HOXB13 is a key lineage homeobox transcription factor that plays a critical role in the differentiation of the prostate gland. Several studies have suggested that HOXB13 alterations may be involved in prostate cancer development and progression. Despite its potential biological relevance, little is known about the expression of HOXB13 across the disease spectrum of prostate cancer. To this end, we
-
Mesonephric-like adenocarcinoma harbours characteristic copy number variations and a distinct DNA methylation signature closely related to mesonephric adenocarcinoma of the cervix J. Pathol. (IF 7.3) Pub Date : 2023-10-18 Felix KF Kommoss, Cheng-Han Lee, Basile Tessier-Cloutier, C Blake Gilks, Colin JR Stewart, Andreas von Deimling, Martin Köbel
Mesonephric-like adenocarcinoma (MLA) of the female genital tract is an uncommon histotype that can arise in both the endometrium and the ovary. The exact cell of origin and histogenesis currently remain unknown. Here, we investigated whole genome DNA methylation patterns and copy number variations (CNVs) in a series of MLAs in the context of a large cohort of various gynaecological carcinoma types
-
Causality and functional relevance of BRCA1 and BRCA2 pathogenic variants in non-high-grade serous ovarian carcinomas J. Pathol. (IF 7.3) Pub Date : 2023-10-18 CJH Kramer, L Lanjouw, D Ruano, A ter Elst, G Santandrea, N Solleveld-Westerink, N Werner, AH van der Hout, CD de Kroon, T van Wezel, LPV Berger, M Jalving, J Wesseling, VTHBM Smit, GH de Bock, CJ van Asperen, MJE Mourits, MPG Vreeswijk, J Bart, T Bosse
The identification of causal BRCA1/2 pathogenic variants (PVs) in epithelial ovarian carcinoma (EOC) aids the selection of patients for genetic counselling and treatment decision-making. Current recommendations therefore stress sequencing of all EOCs, regardless of histotype. Although it is recognised that BRCA1/2 PVs cluster in high-grade serous ovarian carcinomas (HGSOC), this view is largely unsubstantiated
-
High-resolution and quantitative spatial analysis reveal intra-ductal phenotypic and functional diversification in pancreatic cancer J. Pathol. (IF 7.3) Pub Date : 2023-10-16 Ellis Michiels, Hediel Madhloum, Silke Van Lint, Nouredin Messaoudi, Rastislav Kunda, Sandrina Martens, Philippe Giron, Catharina Olsen, Pierre Lefesvre, Nelson Dusetti, Leila EL Mohajer, Richard Tomasini, Lukas JAC Hawinkels, Farah Ahsayni, Rémy Nicolle, Tatjana Arsenijevic, Christelle Bouchart, Jean-Luc Van Laethem, Ilse Rooman
A ‘classical’ and a ‘basal-like’ subtype of pancreatic cancer have been reported, with differential expression of GATA6 and different dosages of mutant KRAS. We established in situ detection of KRAS point mutations and mRNA panels for the consensus subtypes aiming to project these findings to paraffin-embedded clinical tumour samples for spatial quantitative analysis. We unveiled that, next to inter-patient
-
Meflin is a marker of pancreatic stellate cells involved in fibrosis and epithelial regeneration in the pancreas J. Pathol. (IF 7.3) Pub Date : 2023-10-05 Ryota Ando, Yukihiro Shiraki, Yuki Miyai, Hiroki Shimizu, Kazuhiro Furuhashi, Shun Minatoguchi, Katsuhiro Kato, Akira Kato, Tadashi Iida, Yasuyuki Mizutani, Kisuke Ito, Naoya Asai, Shinji Mii, Nobutoshi Esaki, Masahide Takahashi, Atsushi Enomoto
Pancreatic stellate cells (PSCs) are stromal cells in the pancreas that play an important role in pancreatic pathology. In chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC), PSCs are known to get activated to form myofibroblasts or cancer-associated fibroblasts (CAFs) that promote stromal fibroinflammatory reactions. However, previous studies on PSCs were mainly based on the findings
-
TRIM28 inactivation in epithelial nephroblastoma is frequent and often associated with predisposing TRIM28 germline variants J. Pathol. (IF 7.3) Pub Date : 2023-10-04 Jenny Wegert, Anne Kristin Fischer, Balazs Palhazi, Taryn D Treger, Cäcilia Hilgers, Barbara Ziegler, Hyunchul Jung, Eva Jüttner, Andreas Waha, Jörg Fuchs, Steven W Warmann, Michael C Frühwald, Jochen Hubertus, Kathy Pritchard-Jones, Norbert Graf, Sam Behjati, Rhoikos Furtwängler, Manfred Gessler, Christian Vokuhl
Wilms tumors (WTs) are histologically diverse childhood cancers with variable contributions of blastema, stroma, and epithelia. A variety of cancer genes operate in WTs, including the tripartite-motif-containing-28 gene (TRIM28). Case reports and small case series suggest that TRIM28 mutations are associated with epithelial morphology and WT predisposition. Here, we systematically investigated the
-
Cellular senescence in kidney biopsies is associated with tubular dysfunction and predicts CKD progression in childhood cancer patients with karyomegalic interstitial nephropathy J. Pathol. (IF 7.3) Pub Date : 2023-10-04 Sebastiaan N Knoppert, Mandy G Keijzer-Veen, Floris A Valentijn, Marry M van den Heuvel-Eibrink, Marc R Lilien, Gerrit van den Berg, Lianne M Haveman, Marijn F Stokman, Geert O Janssens, Sven van Kempen, Roel Broekhuizen, Roel Goldschmeding, Tri Q Nguyen
Karyomegalic interstitial nephropathy (KIN) has been reported as an incidental finding in patients with childhood cancer treated with ifosfamide. It is defined by the presence of tubular epithelial cells (TECs) with enlarged, irregular, and hyperchromatic nuclei. Cellular senescence has been proposed to be involved in kidney fibrosis in hereditary KIN patients. We report that KIN could be diagnosed
-
Cell-type-specific tumour sensitivity identified with a bromodomain targeting PROTAC in adenoid cystic carcinoma J. Pathol. (IF 7.3) Pub Date : 2023-10-04 Alexandra J Rose, Mercedes M Fleming, Jeffrey C Francis, Jian Ning, Anton Patrikeev, Ritika Chauhan, Kevin J Harrington, Amanda Swain
Salivary gland adenoid cystic carcinoma (ACC) is a rare malignancy with limited treatment options. The development of novel therapies is hindered by a lack of preclinical models. We have generated ACC patient-derived xenograft (PDX) lines that retain the physical and genetic properties of the original tumours, including the presence of the common MYB::NFIB or MYBL1::NFIB translocations. We have developed
-
Transcriptomics and proteomics reveal distinct biology for lymph node metastases and tumour deposits in colorectal cancer J. Pathol. (IF 7.3) Pub Date : 2023-10-04 Nelleke PM Brouwer, Loth Webbink, Tariq S Haddad, Natasja Rutgers, Shannon van Vliet, Colin S Wood, Pascal WTC Jansen, Maxime W Lafarge, , Johannes HW de Wilt, Niek Hugen, Femke Simmer, Nigel B Jamieson, Daniele VF Tauriello, Viktor H Kölzer, Michiel Vermeulen, Iris D Nagtegaal
Both lymph node metastases (LNMs) and tumour deposits (TDs) are included in colorectal cancer (CRC) staging, although knowledge regarding their biological background is lacking. This study aimed to compare the biology of these prognostic features, which is essential for a better understanding of their role in CRC spread. Spatially resolved transcriptomic analysis using digital spatial profiling was
-
Initial interactions with the FDA on developing a validation dataset as a medical device development tool J. Pathol. (IF 7.3) Pub Date : 2023-10-04 Steven Hart, Victor Garcia, Sarah N Dudgeon, Matthew G Hanna, Xiaoxian Li, Kim RM Blenman, Katherine Elfer, Amy Ly, Roberto Salgado, Joel Saltz, Rajarsi Gupta, Evangelos Hytopoulos, Denis Larsimont, Jochen Lennerz, Brandon D Gallas
Quantifying tumor-infiltrating lymphocytes (TILs) in breast cancer tumors is a challenging task for pathologists. With the advent of whole slide imaging that digitizes glass slides, it is possible to apply computational models to quantify TILs for pathologists. Development of computational models requires significant time, expertise, consensus, and investment. To reduce this burden, we are preparing