-
ΔNp73 and its effector targets promote colorectal peritoneal carcinosis and predict survival J. Pathol. (IF 7.3) Pub Date : 2024-04-17 Daniel Pastor‐Morate, Lidia Amigo‐Morán, María Garranzo‐Asensio, Raquel Rejas‐González, Patricia Carnicero, Nuria Rodríguez, Juan Pedro Pérez‐Robledo, Rodrigo Barderas, Isabel Prieto‐Nieto, Gemma Domínguez
Peritoneal metastasis of colorectal origin appears in ~10–15% of patients at the time of diagnosis and in 30–40% of cases with disease progression. Locoregional spread through the peritoneum is considered stage IVc and is associated with a poor prognosis. The development of a regional therapeutic strategy based on cytoreductive surgery, and hyperthermic intra‐abdominal chemotherapy has significantly
-
RAF1 gene fusions are recurrent driver events in infantile fibrosarcoma‐like mesenchymal tumors J. Pathol. (IF 7.3) Pub Date : 2024-04-17 Marialetizia Motta, Sabina Barresi, Simone Pizzi, Delfina Bifano, Jennifer Lopez Marti, Marta Garrido‐Pontnou, Elisabetta Flex, Alessandro Bruselles, Isabella Giovannoni, Giovannina Rotundo, Alessandra Fragale, Valentina Tirelli, Silvia Vallese, Andrea Ciolfi, Gianni Bisogno, Rita Alaggio, Marco Tartaglia
Infantile fibrosarcomas (IFS) and congenital mesoblastic nephroma (CMN) are rare myofibroblastic tumors of infancy and early childhood commonly harboring the ETV6::NTRK3 gene fusion. IFS/CMN are considered as tumors with an ‘intermediate prognosis’ as they are locally aggressive, but rarely metastasize, and generally have a favorable outcome. A fraction of IFS/CMN‐related neoplasms are negative for
-
Acquired NF2 mutation confers resistance to TRK inhibition in an ex vivoLMNA::NTRK1‐rearranged soft‐tissue sarcoma cell model J. Pathol. (IF 7.3) Pub Date : 2024-04-13 Yanjiang Chen, Sabrina Steiner, Catherine Hagedorn, Sarah Kollar, Alicia Pliego‐Mendieta, Martina Haberecker, Jan Plock, Christian Britschgi, Lara Planas‐Paz, Chantal Pauli
Genomic rearrangements of the neurotrophic receptor tyrosine kinase genes (NTRK1, NTRK2, and NTRK3) are the most common mechanism of oncogenic activation for this family of receptors, resulting in sustained cancer cell proliferation. Several targeted therapies have been approved for tumours harbouring NTRK fusions and a new generation of TRK inhibitors has already been developed due to acquired resistance
-
Enhanced prostatic Esr1+ luminal epithelial cells in the absence of SRD5A2 J. Pathol. (IF 7.3) Pub Date : 2024-04-12 Christina Sharkey, Xingbo Long, Ra'ad Al‐Faouri, Douglas Strand, Aria F Olumi, Zongwei Wang
Steroid 5α reductase 2 (SRD5A2) converts testosterone to dihydrotestosterone and is crucial for prostatic development. 5α reductase inhibitors (5ARI) reduce prostate size in benign prostate hyperplasia (BPH) and ameliorate lower urinary tract symptoms secondary to BPH. However, the mechanisms of 5ARI functioning are still not fully understood. Here, we used a Srd5a2−/− mouse model and employed single‐cell
-
TGF‐β3 from fibroblasts promotes necrotising sialometaplasia by suppressing salivary gland cell proliferation and inducing squamous metaplasia J. Pathol. (IF 7.3) Pub Date : 2024-04-10 Shohei Yoshimoto, Naomi Yada, Ayataka Ishikawa, Kenji Kawano, Kou Matsuo, Akimitsu Hiraki, Kazuhiko Okamura
Necrotising sialometaplasia (NSM) is a non‐neoplastic lesion mainly arising in the minor salivary glands of the oral cavity. In the clinical features, NSM shows swelling with or without ulceration, and can mimic a malignant disease such as squamous cell carcinoma. Histopathologically, NSM usually shows the lobular architecture that is observed in the salivary glands. Additionally, acinar infarction
-
From morphology to methylome: epigenetic studies of Müllerian mesonephric‐like adenocarcinoma reveal similarities to cervical mesonephric adenocarcinoma† J. Pathol. (IF 7.3) Pub Date : 2024-04-09 Lawrence H Lin, Brooke E Howitt, David L Kolin
Mesonephric adenocarcinomas (MAs) and mesonephric‐like adenocarcinomas (MLAs) are rare, aggressive neoplasms that arise in the gynecologic tract and show overlapping morphologic, immunohistochemical, and molecular features. While MAs occur in the cervix and are thought to arise from mesonephric remnants, MLAs occur in the endometrium and ovary and are believed to originate from transdifferentiation
-
Co‐targeting BET, CBP, and p300 inhibits neuroendocrine signalling in androgen receptor‐null prostate cancer J. Pathol. (IF 7.3) Pub Date : 2024-04-05 Nicholas Choo, Shivakumar Keerthikumar, Susanne Ramm, Daisaku Ashikari, Linda Teng, Birunthi Niranjan, Shelley Hedwards, Laura H Porter, David L Goode, Kaylene J Simpson, Renea A Taylor, Gail P Risbridger, Mitchell G Lawrence
There are diverse phenotypes of castration‐resistant prostate cancer, including neuroendocrine disease, that vary in their sensitivity to drug treatment. The efficacy of BET and CBP/p300 inhibitors in prostate cancer is attributed, at least in part, to their ability to decrease androgen receptor (AR) signalling. However, the activity of BET and CBP/p300 inhibitors in prostate cancers that lack the
-
Cell division‐dependent dissemination following E‐cadherin loss underlies initiation of diffuse‐type gastric cancer J. Pathol. (IF 7.3) Pub Date : 2024-04-04 Jooske L Monster, Lars JS Kemp, Georg A Busslinger, Marjolein J Vliem, Lucca LM Derks, Annelot AL Staes, Tanya M Bisseling, Hans Clevers, Rachel S van der Post, Martijn Gloerich
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
-
-
Obliteration of portal venules contributes to portal hypertension in biliary cirrhosis J. Pathol. (IF 7.3) Pub Date : 2024-03-29 Shan Shan, Xinyan Zhao, Michelle A Wood‐Trageser, Doudou Hu, Liwei Liu, Beining Qi, Jianbo Jian, Ping Wang, Wenjuan Lv, Chunhong Hu
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, n = 63), primary biliary cholangitis (PBC, n = 18), and hepatitis
-
UPK3A+ umbrella cell damage mediated by TLR3–NR2F6 triggers programmed destruction of urothelium in Hunner‐type interstitial cystitis/painful bladder syndrome J. Pathol. (IF 7.3) Pub Date : 2024-03-29 Liao Peng, Jia‐Wei Chen, Yuan‐Zhuo Chen, Chi Zhang, Si‐Hong Shen, Meng‐Zhu Liu, Yang Fan, Shi‐Qin Yang, Xiu‐Zhen Zhang, Wei Wang, Xiao‐Shuai Gao, Xing‐Peng Di, Yu‐Cheng Ma, Xiao Zeng, Hong Shen, Xi Jin, De‐Yi Luo
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
-
Polyketide synthase positive Escherichia coli one‐time measurement in stool is not informative of colorectal cancer risk in a screening setting J. Pathol. (IF 7.3) Pub Date : 2024-03-29 Willemijn de Klaver, Meike de Wit, Anne Bolijn, Marianne Tijssen, Pien Delis‐van Diemen, Margriet Lemmens, Manon CW Spaander, Evelien Dekker, Monique E van Leerdam, Veerle MH Coupé, Ruben van Boxtel, Hans Clevers, Beatriz Carvalho, Gerrit A Meijer
Environmental factors like the pathogenicity island polyketide synthase positive (pks+) Escherichia coli (E. coli) could have potential for risk stratification in colorectal cancer (CRC) screening. The association between pks+ E. coli measured in fecal immunochemical test (FIT) samples and the detection of advanced neoplasia (AN) at colonoscopy was investigated. Biobanked FIT samples were analyzed
-
Research autopsy programmes in oncology: shared experience from 14 centres across the world J. Pathol. (IF 7.3) Pub Date : 2024-03-29 Tatjana Geukens, Marion Maetens, Jody E Hooper, Steffi Oesterreich, Adrian V Lee, Lori Miller, Jenny M Atkinson, Margaret Rosenzweig, Shannon Puhalla, Heather Thorne, Lisa Devereux, David Bowtell, Sherene Loi, Eliza R Bacon, Kena Ihle, Mihae Song, Lorna Rodriguez‐Rodriguez, Alana L Welm, Lisa Gauchay, Rajmohan Murali, Pharto Chanda, Ali Karacay, Cristina Naceur‐Lombardelli, Hayley Bridger, Charles
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
-
Automated tumor immunophenotyping predicts clinical benefit from anti‐PD‐L1 immunotherapy J. Pathol. (IF 7.3) Pub Date : 2024-03-25 Xiao Li, Jeffrey Eastham, Jennifer M Giltnane, Wei Zou, Andries Zijlstra, Evgeniy Tabatsky, Romain Banchereau, Ching‐Wei Chang, Barzin Y Nabet, Namrata S Patil, Luciana Molinero, Steve Chui, Maureen Harryman, Shari Lau, Linda Rangell, Yannick Waumans, Mark Kockx, Darya Orlova, Hartmut Koeppen
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
-
Correction to ‘Autophagy mediates survival of pancreatic tumour‐initiating cells in a hypoxic microenvironment’ J. Pathol. (IF 7.3) Pub Date : 2024-03-21
Vanessa Rausch, Li Liu, Anja Apel, Theresa Rettig, Jury Gladkich, Sabrina Labsch, Georgios Kallifatidis, Adam Kaczorowski, Ariane Groth, Wolfgang Gross, Martha M Gebhard, Peter Schemmer, Jens Werner, Alexei V Salnikov, Hanswalter Zentgraf, Markus W Büchler and Ingrid Herr. J Pathol 2012; 227: 325–335. https://doi.org/10.1002/path.3994 The corresponding author informed the editors of an error in Figure
-
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 : 2024-02-25 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
-
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
-
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
-
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
-
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
-
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
-
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