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A novel telomere biology disease-associated gastritis identified through a whole exome sequencing-driven approach. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-11-22 Namrata Setia,Daniela Del Gaudio,Priscilla Kandikatla,Kelly Arndt,Melissa Tjota,Peng Wang,Jeremy Segal,Mir Alikhan,John Hart
A whole exome sequencing (WES)-driven approach to uncover the etiology of unexplained inflammatory gastritides has been underutilized by surgical pathologists. Here, we discovered the pathobiology of an unusual chronic atrophic gastritis in two unrelated patients using this approach. The gastric biopsies were notable for an unusual pattern of gastritis with persistent dense inflammation, loss of both
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Low-burden TP53 mutations represent frequent genetic events in CLL with an increased risk for treatment initiation. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-11-21 Tamás László,Lili Kotmayer,Viktória Fésüs,Lajos Hegyi,Stefánia Gróf,Ákos Nagy,Béla Kajtár,Alexandra Balogh,Júlia Weisinger,Tamás Masszi,Zsolt Nagy,Péter Farkas,Judit Demeter,Ildikó Istenes,Róbert Szász,Lajos Gergely,Adrienn Sulák,Zita Borbényi,Dóra Lévai,Tamás Schneider,Piroska Pettendi,Emese Bodai,László Szerafin,László Rejtő,Árpád Bátai,Mária Á Dömötör,Hermina Sánta,Márk Plander,Tamás Szendrei,Aryan
TP53 aberrations predict chemoresistance and represent a contraindication for the use of standard chemoimmunotherapy in chronic lymphocytic leukaemia (CLL). Recent next-generation sequencing (NGS)-based studies have identified frequent low-burden TP53 mutations with variant allele frequencies below 10%, but the clinical impact of these low-burden TP53 mutations is still a matter of debate. In this
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Immunohistochemical characteristics and potential therapeutic regimens of hepatoid adenocarcinoma of the stomach: a study of 139 cases. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-11-16 Xuesong Yang,Yan Wu,Anqiang Wang,Xiuli Ma,Kai Zhou,Ke Ji,Xin Ji,Ji Zhang,Xiaojiang Wu,ZhongWu Li,Zhaode Bu
Hepatoid adenocarcinoma of stomach (HAS) is a special subtype of gastric cancer with poor prognosis. Immunohistochemical analysis could provide important clues for the treatment of HAS. A total of 159 patients were diagnosed as HAS and 139 were enrolled in this study. Statistical differences were determined using relative test methods and survival analyses were performed by the Kaplan-Meier method
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Copy number loss of KDM5D may be a predictive biomarker for ATR inhibitor treatment in male patients with pulmonary squamous cell carcinoma. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-11-16 Ayako Ura,Takuo Hayashi,Kazumasa Komura,Masaki Hosoya,Kazuya Takamochi,Eiichi Sato,Satomi Saito,Susumu Wakai,Takafumi Handa,Tsuyoshi Saito,Shunsuke Kato,Kenji Suzuki,Takashi Yao,
A limited number of patients with lung squamous cell carcinoma (SCC) benefit clinically from molecular targeted drugs because of a lack of targetable driver alterations. We aimed to understand the prevalence and clinical significance of lysine-specific demethylase 5D (KDM5D) copy number loss in SCC and explore its potential as a predictive biomarker for ataxia-telangiectasia and Rad3-related (ATR)
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Engineering the future of 3D pathology. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-11-02 Jonathan Tc Liu,Sarah Sl Chow,Richard Colling,Michelle R Downes,Xavier Farré,Peter Humphrey,Andrew Janowczyk,Tuomas Mirtti,Clare Verrill,Inti Zlobec,Lawrence D True
In recent years, technological advances in tissue preparation, high-throughput volumetric microscopy, and computational infrastructure have enabled rapid developments in nondestructive 3D pathology, in which high-resolution histologic datasets are obtained from thick tissue specimens, such as whole biopsies, without the need for physical sectioning onto glass slides. While 3D pathology generates massive
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AI-based intra-tumor heterogeneity score of Ki67 expression as a prognostic marker for early-stage ER+/HER2- breast cancer. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-10-24 Wenqi Lu,Ayat G Lashen,Noorul Wahab,Islam M Miligy,Mostafa Jahanifar,Michael Toss,Simon Graham,Mohsin Bilal,Abhir Bhalerao,Nehal M Atallah,Shorouk Makhlouf,Asmaa Y Ibrahim,David Snead,Fayyaz Minhas,Shan E Ahmed Raza,Emad Rakha,Nasir Rajpoot
Early-stage estrogen receptor positive and human epidermal growth factor receptor negative (ER+/HER2-) luminal breast cancer (BC) is quite heterogeneous and accounts for about 70% of all BCs. Ki67 is a proliferation marker that has a significant prognostic value in luminal BC despite the challenges in its assessment. There is increasing evidence that spatial colocalization, which measures the evenness
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Identifying primary tumor site of origin for liver metastases via a combination of handcrafted and deep learning features. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-10-11 Chuheng Chen,Cheng Lu,Vidya Viswanathan,Brandon Maveal,Bhunesh Maheshwari,Joseph Willis,Anant Madabhushi
Liver is one of the most common sites for metastases, which can occur on account of primary tumors from multiple sites of origin. Identifying the primary site of origin (PSO) of a metastasis can help in guiding therapeutic options for liver metastases. In this pilot study, we hypothesized that computer extracted handcrafted (HC) histomorphometric features can be utilized to identify the PSO of liver
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Expression of B7-H3 and TIM-3 in gastric-type endocervical adenocarcinoma: prevalence, association with PD-L1 expression, and prognostic significance. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-10-05 Yao Sun,Xin Zhou,Elena Lucas,Lili Chen,Huijuan Zhang,Hao Chen,Feng Zhou
Gastric-type endocervical adenocarcinoma (GEA) is the second most common subtype of endocervical adenocarcinoma and has a poor prognosis. Anti-programmed death-1 and anti-programmed death-ligand 1 (PD-L1) inhibitors have emerged as a major treatment option for GEA; however, data on the expression of other immune checkpoints in GEA are limited. We analyzed the expression of T-cell immunoglobulin and
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Digital image analysis allows objective stratification of patients with silent PIT1-lineage pituitary neuroendocrine tumors. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-09-04 Jiangyan Zhao,Chenxing Ji,Haixia Cheng,Zhen Ye,Boyuan Yao,Ming Shen,Xuefei Shou,Xiang Zhou,Hongying Ye,Zhaoyun Zhang,Hong Chen,Yongfei Wang,Fuchu He,Yao Zhao,Wei Gong,Qilin Zhang,Nidan Qiao
Studies describing the clinical presentation and prognosis of patients with silent PIT1 (pituitary specific transcription factor)-lineage pituitary neuroendocrine tumors (PitNETs) are rare. We identified patients with positive PIT1 tumor staining but without evidence of hormone hypersecretion at a tertiary center. Clusters were obtained according to cell morphology and immunostaining from each patient's
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High expression of insulinoma-associated protein 1 (INSM1) distinguishes colorectal mixed and pure neuroendocrine carcinomas from conventional adenocarcinomas with diffuse expression of synaptophysin. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-08-22 Anne-Sophie Litmeyer,Björn Konukiewitz,Atsuko Kasajima,Sebastian Foersch,Felix Schicktanz,Maxime Schmitt,Franziska Kellers,Albert Grass,Paul Jank,Bettina Lehman,Thomas M Gress,Anja Rinke,Detlef K Bartsch,Carsten Denkert,Wilko Weichert,Günter Klöppel,Moritz Jesinghaus
Complementary to synaptophysin and chromogranin A, insulinoma-associated protein 1 (INSM1) has emerged as a sensitive marker for the diagnosis of neuroendocrine neoplasms. Since there are no comparative data regarding INSM1 expression in conventional colorectal adenocarcinomas (CRCs) and colorectal mixed adenoneuroendocrine carcinomas/neuroendocrine carcinomas (MANECs/NECs), we examined INSM1 in a
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Translational practice of fluorescence in situ hybridisation to identify neuroblastic tumours with TERT rearrangements. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-08-22 Yongbo Yu,Meng Zhang,Xingfeng Yao,Xiaoxing Guan,Chao Jia,Ping Chu,Ruqian Zhang,Yeran Yang,Yaqiong Jin,Huanmin Wang,Xin Ni,Lejian He,Yongli Guo
Recently, telomerase reverse transcriptase (TERT) gene rearrangements have been identified in neuroblastoma (NB), the typical pathological type of neuroblastic tumours (NTs); however, the prevalence of TERT rearrangements in other types of NT remains unknown. This study aimed to develop a practical method for detecting TERT defects and to evaluate the clinical relevance of TERT rearrangements as a
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DNA methylation profile discriminates sporadic giant cell granulomas of the jaws and cherubism from their giant cell-rich histological mimics. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-08-09 Letícia Martins Guimarães,Daniel Baumhoer,Vanghelita Andrei,Dennis Friedel,Christian Koelsche,Ricardo Santiago Gomez,Andreas von Deimling,Carolina Cavalieri Gomes
Sporadic giant cell granulomas (GCGs) of the jaws and cherubism-associated giant cell lesions share histopathological features and microscopic diagnosis alone can be challenging. Additionally, GCG can morphologically closely resemble other giant cell-rich lesions, including non-ossifying fibroma (NOF), aneurysmal bone cyst (ABC), giant cell tumour of bone (GCTB), and chondroblastoma. The epigenetic
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RAD51 as a biomarker for homologous recombination deficiency in high-grade serous ovarian carcinoma: robustness and interobserver variability of the RAD51 test. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-07-28 Claire Jh Kramer,Alba Llop-Guevara,Elisa Yaniz-Galende,Benedetta Pellegrino,Natalja T Ter Haar,Andrea Herencia-Ropero,Nicoletta Campanini,Antonino Musolino,Tjalling Bosse,Alexandra Leary,Violeta Serra,Maaike Pg Vreeswijk
The RAD51 test is emerging as a promising biomarker for the assessment of functional homologous recombination deficiency (HRD). Yet, the robustness and reproducibility of the immunofluorescence-based RAD51 test, in different academic laboratories, have not been systematically investigated. Therefore, we tested the performance of the RAD51 assay in formalin-fixed paraffin-embedded (FFPE) high-grade
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The epigenetic modifier lysine methyltransferase 2C is frequently mutated in gastric remnant carcinoma. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-07-03 Bo Sun,Haojie Chen,Jiawen Lao,Cong Tan,Yue Zhang,Zhen Shao,Dazhi Xu
Gastric remnant carcinoma (GRC), which occurs in the stomach after partial gastrectomy, is a rare and aggressive form of gastric adenocarcinoma (GAC). Comprehensive profiling of genomic mutations in GRC could provide the basis for elucidating the origin and characteristics of this cancer. Herein, whole-exome sequencing (WES) was performed on 36 matched tumor-normal samples from patients with GRC and
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Cancer-associated fibroblast expression of glutamine fructose-6-phosphate aminotransferase 2 (GFPT2) is a prognostic marker in gastric cancer. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-07-03 Shuo Yang,Guoli Li,Xin Yin,Yufei Wang,Xinju Jiang,Xiulan Bian,Tianyi Fang,Shengjie Yin,Lei Zhang,Yingwei Xue
Glutamine fructose-6-phosphate aminotransferase 2 (GFPT2) is a rate-limiting enzyme in hexosamine biosynthesis involved in the occurrence and progress of many cancers. What role it plays in gastric cancer (GC) is still unclear. In this study, transcriptome sequencing data from the Harbin Medical University (HMU)-GC cohort and The Cancer Genome Atlas (TCGA) dataset were combined with the HMU-TCGA training
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Exosome-derived ANXA9 functions as an oncogene in breast cancer. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-06-09 Cuiping Lu,Ying Zhan,Yunshan Jiang,Jianrong Liao,Zidan Qiu
Breast cancer (BCA) is one of the most prevalent cancers among women. Emerging evidence has revealed that Annexin A-9 (ANXA9) plays a crucial function in the development of some cancers. Notably, ANXA9 has been reported to be a new prognostic biomarker for gastric and colorectal cancers. However, its expression and biological function in BCA have not yet been investigated. Using online bioinformatics
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Post-operative mortality and recurrence patterns in pancreatic cancer according to KRAS mutation and CDKN2A, p53, and SMAD4 expression. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-06-08 Yohei Masugi,Manabu Takamatsu,Mariko Tanaka,Kensuke Hara,Yosuke Inoue,Tsuyoshi Hamada,Tatsunori Suzuki,Junichi Arita,Yuki Hirose,Yoshikuni Kawaguchi,Yousuke Nakai,Atsushi Oba,Naoki Sasahira,Gaku Shimane,Tsuyoshi Takeda,Keisuke Tateishi,Sho Uemura,Mitsuhiro Fujishiro,Kiyoshi Hasegawa,Minoru Kitago,Yu Takahashi,Tetsuo Ushiku,Kengo Takeuchi,Michiie Sakamoto,
Alterations in KRAS, CDKN2A (p16), TP53, and SMAD4 genes have been major drivers of pancreatic carcinogenesis. The clinical course of patients with pancreatic cancer in relation to these driver alterations has not been fully characterised in large populations. We hypothesised that pancreatic carcinomas with different combinations of KRAS mutation and aberrant expression of CDKN2A, p53, and SMAD4 might
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Dual epigenetic changes in diabetes mellitus-associated pancreatic ductal adenocarcinoma correlate with downregulation of E-cadherin and worsened prognosis. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-05-28 Yutaro Hara,Hiroki Mizukami,Keisuke Yamazaki,Takahiro Yamada,Akiko Igawa,Yuki Takeuchi,Takanori Sasaki,Hanae Kushibiki,Kotaro Murakami,Kazuhiro Kudoh,Keinosuke Ishido,Kenichi Hakamada
Diabetes mellitus (DM) is a risk factor for pancreatic ductal adenocarcinoma (PDAC) that promotes the promoter methylation of CDH1. It is still unclear whether DM can exert other epigenetic effects, such as altering microRNA (miR) expression, in PDAC. The expression of miR-100-5p is known to be changed in DM patients and can suppress the expression of E-cadherin. In this study, the correlation between
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KLF2 inhibits colorectal cancer progression and metastasis by inducing ferroptosis via the PI3K/AKT signaling pathway. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-05-06 Jia Li,Ji Ling Jiang,Yi Mei Chen,Wei Qi Lu
Krüppel-like factor 2 (KLF2) belongs to the zinc finger family and is thought to be a tumor suppressor gene due to its low expression in various cancer types. However, its functional role and molecular pathway involvement in colorectal cancer (CRC) are not well defined. Herein, we investigated the potential mechanism of KLF2 in CRC cell invasion, migration, and epithelial-mesenchymal transition (EMT)
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NTRK gene aberrations in triple-negative breast cancer: detection challenges using IHC, FISH, RT-PCR, and NGS. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-05-04 Federica Zito Marino,Simona Buono,Marco Montella,Rosa Giannatiempo,Francesco Messina,Giovanni Casaretta,Grazia Arpino,Giulia Vita,Francesco Fiorentino,Luigi Insabato,Alessandro Sgambato,Michele Orditura,Renato Franco,Marina Accardo
Triple-negative breast cancer (TNBC) is usually an aggressive disease with a poor prognosis and limited treatment options. The neurotrophic tyrosine receptor kinase (NTRK) gene fusions are cancer type-agnostic emerging biomarkers approved by the Food and Drug Administration (FDA), USA, for the selection of patients for targeted therapy. The main aim of our study was to investigate the frequency of
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Defining triple-negative breast cancer with neuroendocrine differentiation (TNBC-NED). J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-04-20 Sean M Hacking,Evgeny Yakirevich,Yihong Wang
Primary breast neuroendocrine (NE) neoplasms are uncommon, and definitions harbor controversy. We retrospectively collected 73 triple-negative breast cancers (TNBC) and evaluated NE biomarker expression along with p53 aberrant staining (which correlates with TP53 gene mutation) and Rb protein loss by immunohistochemistry. In the study cohort, we found 11 (15%) cases of TNBC with neuroendocrine differentiation
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Cell-by-cell quantification of the androgen receptor in benign and malignant prostate leads to a better understanding of changes linked to cancer initiation and progression. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-04-18 Seta Derderian,Tarik Benidir,Eleonora Scarlata,Turki Altaylouni,Lucie Hamel,Fatima Zahra Zouanat,Fadi Brimo,Armen Aprikian,Simone Chevalier
The androgen receptor (AR) plays a crucial role in the development and homeostasis of the prostate and is a key therapeutic target in prostate cancer (PCa). The gold standard therapy for advanced PCa is androgen deprivation therapy (ADT), which targets androgen production and AR signaling. However, resistance to ADT develops via AR-dependent and AR-independent mechanisms. As reports on AR expression
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Explainability and causability in digital pathology. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-04-12 Markus Plass,Michaela Kargl,Tim-Rasmus Kiehl,Peter Regitnig,Christian Geißler,Theodore Evans,Norman Zerbe,Rita Carvalho,Andreas Holzinger,Heimo Müller
The current move towards digital pathology enables pathologists to use artificial intelligence (AI)-based computer programmes for the advanced analysis of whole slide images. However, currently, the best-performing AI algorithms for image analysis are deemed black boxes since it remains - even to their developers - often unclear why the algorithm delivered a particular result. Especially in medicine
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Altered cytoplasmic and nuclear ADP-ribosylation levels analyzed with an improved ADP-ribose binder are a prognostic factor in renal cell carcinoma. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-03-31 Peter Schraml,Fabio Aimi,Martin Zoche,Domingo Aguilera-Garcia,Fabian Arnold,Holger Moch,Michael O Hottiger
ADP-ribosylation (ADPR) of proteins is catalyzed by ADP-ribosyltransferases, which are targeted by inhibitors (i.e. poly(ADP-ribose) polymerase inhibitors [PARPi]). Although renal cell carcinoma (RCC) cells are sensitive in vitro to PARPi, studies on the association between ADPR levels and somatic loss of function mutations in DNA damage repair genes are currently missing. Here we observed, in two
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KRAS mutations and endometriosis burden of disease. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-03-28 Natasha L Orr,Arianne Albert,Yang Doris Liu,Amy Lum,JooYoon Hong,Catalina L Ionescu,Janine Senz,Tayyebeh M Nazeran,Anna F Lee,Heather Noga,Kate Lawrenson,Catherine Allaire,Christina Williams,Mohamed A Bedaiwy,Michael S Anglesio,Paul J Yong
The clinical phenotype of somatic mutations in endometriosis is unknown. The objective was to determine whether somatic KRAS mutations were associated with greater disease burden in endometriosis (i.e. more severe subtypes and higher stage). This prospective longitudinal cohort study included 122 subjects undergoing endometriosis surgery at a tertiary referral center between 2013 and 2017, with 5-9 years
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p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-03-22 Martin Köbel,Eun-Young Kang,Ashley Weir,Peter F Rambau,Cheng-Han Lee,Gregg S Nelson,Prafull Ghatage,Nicola S Meagher,Marjorie J Riggan,Jennifer Alsop,Michael S Anglesio,Matthias W Beckmann,Christiani Bisinotto,Michelle Boisen,Jessica Boros,Alison H Brand,Angela Brooks-Wilson,Michael E Carney,Penny Coulson,Madeleine Courtney-Brooks,Kara L Cushing-Haugen,Cezary Cybulski,Suha Deen,Mona A El-Bahrawy,Esther
Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented
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Identification and validation of NFIA as a novel prognostic marker in renal cell carcinoma. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-03-22 Roger de Alwis,Sarah Schoch,Mazharul Islam,Christina Möller,Börje Ljungberg,Håkan Axelson
Prognostic tools are an essential component of the clinical management of patients with renal cell carcinoma (RCC). Although tumour stage and grade can provide important information, they fail to consider patient- and tumour-specific biology. In this study, we set out to find a novel molecular marker of RCC by using hepatocyte nuclear factor 4A (HNF4A), a transcription factor implicated in RCC progression
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Development of multiple AI pipelines that predict neoadjuvant chemotherapy response of breast cancer using H&E-stained tissues. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-03-10 Bin Shen,Akira Saito,Ai Ueda,Koji Fujita,Yui Nagamatsu,Mikihiro Hashimoto,Masaharu Kobayashi,Aashiq H Mirza,Hans Peter Graf,Eric Cosatto,Shoichi Hazama,Hiroaki Nagano,Eiichi Sato,Jun Matsubayashi,Toshitaka Nagao,Esther Cheng,Syed Af Hoda,Takashi Ishikawa,Masahiko Kuroda
In recent years, the treatment of breast cancer has advanced dramatically and neoadjuvant chemotherapy (NAC) has become a common treatment method, especially for locally advanced breast cancer. However, other than the subtype of breast cancer, no clear factor indicating sensitivity to NAC has been identified. In this study, we attempted to use artificial intelligence (AI) to predict the effect of preoperative
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Low gamma-butyrobetaine dioxygenase (BBOX1) expression as a prognostic biomarker in patients with clear cell renal cell carcinoma: a machine learning approach. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-03-02 Kyu-Shik Kim,Kyoung Min Moon,Kyueng-Whan Min,Woon Yong Jung,Su-Jin Shin,Seung Wook Lee,Mi Jung Kwon,Dong-Hoon Kim,Sukjoong Oh,Yung-Kyun Noh
Gamma-butyrobetaine dioxygenase (BBOX1) is a catalyst for the conversion of gamma-butyrobetaine to l-carnitine, which is detected in normal renal tubules. The purpose of this study was to analyze the prognosis, immune response, and genetic alterations associated with low BBOX1 expression in patients with clear cell renal cell carcinoma (RCC). We analyzed the relative influence of BBOX1 on survival
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The activation of EP300 by F11R leads to EMT and acts as a prognostic factor in triple-negative breast cancers. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-02-13 Chien-Hsiu Li,Chih-Yeu Fang,Ming-Hsien Chan,Pei-Jung Lu,Luo-Ping Ger,Jan-Show Chu,Yu-Chan Chang,Chi-Long Chen,Michael Hsiao
Cancer progression is influenced by junctional adhesion molecule (JAM) family members. The relationship between JAM family members and different types of cancer was examined using The Cancer Genome Atlas dataset. mRNA levels of the F11R (F11 receptor) in tumours were inversely correlated to the expression of JAM-2 and JAM-3. This relationship was unique to breast cancer (BCa) and was associated with
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CD70 and PD-L1 (CD274) co-expression predicts poor clinical outcomes in patients with pleural mesothelioma. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-02-08 Shingo Inaguma,Akane Ueki,Jerzy Lasota,Masayuki Komura,Asraful Nahar Sheema,Piotr Czapiewski,Renata Langfort,Janusz Rys,Joanna Szpor,Piotr Waloszczyk,Krzysztof Okoń,Wojciech Biernat,David S Schrump,Raffit Hassan,Markku Miettinen,Satoru Takahashi
Diffuse pleural mesothelioma (PM) is a highly aggressive tumour typically associated with short survival. Recently, the effectiveness of first-line immune checkpoint inhibitors in patients with unresectable PM was reported. CD70-CD27 signalling plays a co-stimulatory role in promoting T cell expansion and differentiation through the nuclear factor κB (NF-κB) pathway. Conversely, the PD-L1 (CD274)-PD-1
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Predicting microsatellite instability and key biomarkers in colorectal cancer from H&E-stained images: achieving state-of-the-art predictive performance with fewer data using Swin Transformer. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-02-01 Bangwei Guo,Xingyu Li,Miaomiao Yang,Jitendra Jonnagaddala,Hong Zhang,Xu Steven Xu
Many artificial intelligence models have been developed to predict clinically relevant biomarkers for colorectal cancer (CRC), including microsatellite instability (MSI). However, existing deep learning networks require large training datasets, which are often hard to obtain. In this study, based on the latest Hierarchical Vision Transformer using Shifted Windows (Swin Transformer [Swin-T]), we developed
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First proficiency testing for NGS-based and combined NGS- and FISH-based detection of FGFR2 fusions in intrahepatic cholangiocarcinoma. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-01-12 Olaf Neumann,Ulrich Lehmann,Stephan Bartels,Nicole Pfarr,Thomas Albrecht,Katharina Ilm,Jens Christmann,Anna-Lena Volckmar,Hannah Goldschmid,Martina Kirchner,Michael Allgäuer,Maria Walker,Hans Kreipe,Andrea Tannapfel,Wilko Weichert,Peter Schirmacher,Daniel Kazdal,Albrecht Stenzinger
Intrahepatic cholangiocarcinoma harbours druggable genetic lesions including FGFR2 gene fusions. Reliable and accurate detection of these fusions is becoming a critical component of the molecular work-up, but real-world data on the performance of fluorescence in situ hybridisation (FISH) and targeted RNA-based next-generation sequencing (NGS) are very limited. Bridging this gap, we report results of
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CD47 and CD68 expression in breast cancer is associated with tumor-infiltrating lymphocytes, blood vessel invasion, detection mode, and prognosis. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2023-01-04 Ying Chen,Tor Audun Klingen,Hans Aas,Elisabeth Wik,Lars A Akslen
CD47 expressed on tumor cells binds to signal regulatory protein alpha on macrophages, initiating inhibition of phagocytosis. We investigated the relationships between tumor expression of CD47 and CD68 macrophage content, subsets of tumor-infiltrating lymphocytes (TILs), and vascular invasion in breast cancer. A population-based series of 282 cases (200 screen detected and 82 interval patients) from
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A novel NGS-based diagnostic algorithm for classifying multifocal lung adenocarcinomas in pN0M0 patients. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-12-29 Xin Zhang,Xiaoxi Fan,Changbo Sun,Liang Wang,Yuan Miao,Liming Wang,Peng Yang,Yang Xu,Xue Ren,Xue Wu,Shun Xu
The classification of multifocal lung adenocarcinomas (MLAs), including multiple primary lung adenocarcinomas (MPLAs) and intrapulmonary metastases (IPMs), has great clinical significance in staging and treatment determination. However, the application of molecular approaches in pN0M0 MLA diagnosis has not been well investigated. Here, we performed next-generation sequencing (NGS) analysis in 45 pN0M0
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Tropomyosin receptor kinase B (TrkB) signalling: targeted therapy in neurogenic tumours. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-12-19 Yuehua Li,Chengjiang Wei,Wei Wang,Qingfeng Li,Zhi-Chao Wang
Tropomyosin receptor kinase B (TrkB), a transmembrane receptor protein, has been found to play a pivotal role in neural development. This protein is encoded by the neurotrophic receptor tyrosine kinase 2 (NTRK2) gene, and its abnormal activation caused by NTRK2 overexpression or fusion can contribute to tumour initiation, progression, and resistance to therapeutics in multiple types of neurogenic tumours
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Real-life data from standardized preanalytical coding (SPREC) in tissue biobanking and its dual use for sample characterization and process optimization. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-12-08 Magdalena Skoworonska,Annika Blank,Irene Centeno,Caroline Hammer,Aurel Perren,Inti Zlobec,Tilman T Rau
The standardized preanalytical code (SPREC) aggregates warm ischemia (WIT), cold ischemia (CIT), and fixation times (FIT) in a precise format. Despite its growing importance underpinned by the European in vitro diagnostics regulation or broad preanalytical programs by the National Institutes of Health, little is known about its empirical occurrence in biobanked surgical specimen. In several steps,
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Validation of the prognostic value of CD3 and CD8 cell densities analogous to the Immunoscore® by stage and location of colorectal cancer: an independent patient cohort study. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-11-24 Elizabeth Alwers,Jakob N Kather,Matthias Kloor,Alexander Brobeil,Katrin E Tagscherer,Wilfried Roth,Amelie Echle,Efrat L Amitay,Jenny Chang-Claude,Hermann Brenner,Michael Hoffmeister
In addition to the traditional staging system in colorectal cancer (CRC), the Immunoscore® has been proposed to characterize the level of immune infiltration in tumor tissue and as a potential prognostic marker. The aim of this study was to examine and validate associations of an immune cell score analogous to the Immunoscore® with established molecular tumor markers and with CRC patient survival in
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Significance of Siglec-15 expression in colorectal cancer: association with advanced disease stage and fewer tumor-infiltrating lymphocytes. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-11-24 Zhao Lu,Pu Cheng,Fei Huang,Jiyun Li,Bingzhi Wang,Shuangmei Zou,Zhaoxu Zheng,Chunwei Peng
Siglec-15, a novel immune suppressor, is upregulated in many human cancers. The aim of this study was to explore the expression of Siglec-15 in colorectal cancer (CRC), and investigate whether Siglec-15 could be a potential target for cancer immunotherapy in patients with CRC. We performed immunohistochemical analyses of Siglec-15 on a cohort of 805 patients with CRC and made comparisons between clinicopathological
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Deep learning-based image analysis reveals significant differences in the number and distribution of mucosal CD3 and γδ T cells between Crohn's disease and ulcerative colitis. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-11-23 Elin Synnøve Røyset,Henrik P Sahlin Pettersen,Weili Xu,Anis Larbi,Arne K Sandvik,Sonja E Steigen,Ignacio Catalan-Serra,Ingunn Bakke
Colon mucosae of ulcerative colitis (UC) and Crohn's disease (CD) display differences in the number and distribution of immune cells that are difficult to assess by eye. Deep learning-based analysis on whole slide images (WSIs) allows extraction of complex quantitative data that can be used to uncover different inflammatory patterns. We aimed to explore the distribution of CD3 and γδ T cells in colon
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Olfactomedin 4 associates with expression of differentiation markers but not with properties of cancer stemness, EMT nor metastatic spread in colorectal cancer. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-11-08 Stefanie Jaitner,Elise Pretzsch,Jens Neumann,Achim Schäffauer,Matthias Schiemann,Martin Angele,Jörg Kumbrink,Sarah Schwitalla,Florian R Greten,Lydia Brandl,Frederick Klauschen,David Horst,Thomas Kirchner,Andreas Jung
Tumor stem cells play a pivotal role in carcinogenesis and metastatic spread in colorectal cancer (CRC). Olfactomedin 4 (OLFM4) is co-expressed with the established stem cell marker leucine-rich repeat-containing G protein-coupled receptor 5 at the bottom of intestinal crypts and has been suggested as a surrogate for cancer stemness and a biomarker in gastrointestinal tumors associated with prognosis
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pTDP-43 aggregates accumulate in non-central nervous system tissues prior to symptom onset in amyotrophic lateral sclerosis: a case series linking archival surgical biopsies with clinical phenotypic data. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-10-13 Samuel B Pattle,Judi O'Shaughnessy,Owen Kantelberg,Olivia M Rifai,Judith Pate,Kristine Nellany,Nadine Hays,Mark J Arends,Mathew H Horrocks,Fergal M Waldron,Jenna M Gregory
Neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) are traditionally considered strictly neurological disorders. However, clinical presentation is not restricted to neurological systems, and non-central nervous system (CNS) manifestations, particularly gastrointestinal (GI) symptoms, are common. Our objective was to understand
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The prognostic marker elastin correlates with epithelial-mesenchymal transition and vimentin-positive fibroblasts in gastric cancer. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-10-13 Tianyi Fang,Lei Zhang,Xin Yin,Yufei Wang,Xinghai Zhang,Xiulan Bian,Xinju Jiang,Shuo Yang,Yingwei Xue
Elastin (ELN) fibers are essential constituents of the tumor microenvironment of gastric cancer (GC). However, few studies have investigated the clinical prognostic significance of ELN in GC. We screened for molecular markers that were highly related to distant metastasis by transcriptome sequencing. The Cancer Genome Atlas (TCGA) and Harbin Medical University (HMU) validation cohorts were used to
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Follow-up of intraocular retinoblastoma through the quantitative analysis of conserved nuclear DNA sequences in aqueous humor from patients. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-09-23 Maria Cuadrado-Vilanova,Victor Burgueño,Leire Balaguer-Lluna,Rosario Aschero,Helena Castillo-Ecija,Jing Liu,Sara Perez-Jaume,Guillem Pascual-Pasto,Nagore G Olaciregui,Soledad Gomez-Gonzalez,Genoveva Correa,Mariona Suñol,Paula Schaiquevich,François Radvanyi,Cinzia Lavarino,Jaume Mora,Jaume Catala-Mora,Guillermo L Chantada,Angel M Carcaboso
Fundoscopy is the standard method for diagnosis and follow-up of intraocular retinoblastoma, but it is sometimes insufficient to discern whether tumors are inactivated following treatments. In this work, we hypothesized that the amount of conserved nuclear DNA sequences in the cell-free DNA (cfDNA) fraction of the aqueous humor (AH) might complement fundoscopy for retinoblastoma follow-up. To address
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A prognostic six-gene expression risk-score derived from proteomic profiling of the metastatic colorectal cancer secretome. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-09-22 Javier Robles,Laura Pintado-Berninches,Issam Boukich,Beatriz Escudero,Vivian de Los Rios,Rubén A Bartolomé,Marta Jaén,Ángela Martín-Regalado,María Jesús Fernandez-Aceñero,Juan Ignacio Imbaud,José Ignacio Casal
The necessity to accurately predict recurrence and clinical outcome in early stage colorectal cancer (CRC) is critical to identify those patients who may benefit from adjuvant chemotherapy. Here, we developed and validated a gene-based risk-score algorithm for patient stratification and personalised treatment in early stage disease based on alterations in the secretion of metastasis-related proteins
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Cellular dissociation grading on biopsies of pulmonary squamous cell carcinoma provides prognostic information across all stages and is congruent with resection specimen grading. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-09-16 Moritz Jesinghaus,Melanie Boxberg,Maxime Schmitt,Mark Kriegsmann,Alexander Harms,Corinna Lang,Thomas Muley,Hauke Winter,Katharina Kriegsmann,Arne Warth,Albrecht Stenzinger,Carsten Denkert,Hans Hoffmann,Seyer Safi,Wilko Weichert
Grading of squamous cell carcinomas (SCCs) based on tumour budding and cell nest size has been termed cellular dissociation grading (CDG) and was suggested as a robust outcome predictor when assessed in biopsies and resections of various extrapulmonary SCCs. In pulmonary SCC (pSCC), this has so far been shown only for resected cancers. As most lung cancers are inoperable, it is of utmost importance
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CYP2S1 and CYP2W1 expression is associated with patient survival in breast cancer. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-07-28 Radhika Aiyappa-Maudsley,Sarah J Storr,Emad A Rakha,Andrew R Green,Ian O Ellis,Stewart G Martin
The cytochrome P450 family of enzymes metabolise a wide range of compounds and play important roles in breast cancer pathogenesis due to their involvement in estrogen metabolism and the production of carcinogenic metabolites during this process. The orphan CYPs, CYP2S1, and CYP2W1 are reportedly upregulated in breast cancer. However, their expression and association with clinicopathological and survival
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CXCL8 expression is associated with advanced stage, right sidedness, and distinct histological features of colorectal cancer. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-07-25 Kathryn Af Pennel,Jean A Quinn,Colin Nixon,Jitwadee Inthagard,Hester C van Wyk,David Chang,Selma Rebus,,Jennifer Hay,Noori N Maka,Campbell Sd Roxburgh,Paul G Horgan,Donald C McMillan,James H Park,Antonia K Roseweir,Colin W Steele,Joanne Edwards
CXCL8 is an inflammatory chemokine elevated in the colorectal cancer (CRC) tumour microenvironment. CXCR2, the major receptor for CXCL8, is predominantly expressed by neutrophils. In the cancer setting, CXCL8 plays important roles in neutrophil chemotaxis, facilitating angiogenesis, invasion, and metastasis. This study aimed to assess the spatial distribution of CXCL8 mRNA expression in CRC specimens
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Spatial expression of the FGFR2b splice isoform and its prognostic significance in endometrioid endometrial carcinoma. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-07-22 Asmerom T Sengal,Deborah Smith,Cameron E Snell,Samuel Leung,Aline Talhouk,Elizabeth D Williams,Jessica N McAlpine,Pamela M Pollock
Endometrial carcinoma (EC) is the most common gynecological malignancy and fibroblast growth factor receptor 2 (FGFR2) is a frequently dysregulated receptor tyrosine kinase. FGFR2b and FGFR2c are the two main splice isoforms of FGFR2 and are normally localized in epithelial and mesenchymal cells, respectively. Previously, we demonstrated that FGFR2c mRNA expression was associated with aggressive tumor
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Identification and therapeutic evaluation of ALK rearrangements in non-small-cell lung cancer. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-07-18 Ruiying Zhao,Lianying Guo,Bo Zhang,Jikai Zhao,Chan Xiang,Shengnan Chen,Jinchen Shao,Lei Zhu,Min Ye,Yuchen Han
This study aimed to present a comprehensive assessment of anaplastic lymphoma kinase (ALK) rearrangements evaluated by DNA/RNA-based next-generation sequencing (NGS) and Ventana immunohistochemistry (IHC) in patients with non-small-cell lung cancer (NSCLC) and to evaluate the therapeutic outcomes of ALK tyrosine kinase inhibitor (TKI) treatment. We investigated ALK gene fusions in 14,894 patients with
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Paediatric BCOR-associated sarcomas with a novel long spliced internal tandem duplication of BCOR exon 15. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-07-14 Jian Yuan Goh,Chik Hong Kuick,Masahiro Sugiura,Sze Jet Aw,Manli Zhao,Hongfeng Tang,Sandini Gunaratne,Fucun Zhu,Lin Cai,Bin Tean Teh,Paul S Thorner,Kenneth Tou En Chang
Clear cell sarcoma of the kidney (CCSK) and primitive myxoid mesenchymal tumour of infancy (PMMTI) are paediatric sarcomas that most commonly harbour internal tandem duplications (ITDs) of exon 15 of the BCOR gene, in the range of 87-114 base pairs (bp). Some cases, instead, have BCOR-CCNB3 or YWHAE-NUTM2 gene fusions. About 10% of cases lack any of these genetic alterations when tested by standard
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A combination of stromal PD-L1 and tumoral nuclear β-catenin expression as an indicator of colorectal carcinoma progression and resistance to chemoradiotherapy in locally advanced rectal carcinoma. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-06-27 Hiroyuki Takahashi,Hirono Watanabe,Miki Hashimura,Toshihide Matsumoto,Ako Yokoi,Mayu Nakagawa,Yu Ishibashi,Takashi Ito,Kensuke Ohhigata,Makoto Saegusa
Programmed cell death-1 (PD-1) and its ligand (PD-L1) are significant mediators of immune suppression in the tumor microenvironment. We focused on the immunological impact of PD-1/PD-L1 signaling during tumor progression in colorectal carcinoma (CRC) and its association with resistance to neoadjuvant chemoradiotherapy (NCRT) in locally advanced rectal carcinoma (LAd-RC). Histopathological and immunohistochemical
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Decreased CD11c-positive dendritic cells in the tumor microenvironment predict double-hit/triple-hit genotype and survival in diffuse large B-cell lymphoma. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-06-17 Chang-Tsu Yuan,Shih-Sung Chuang,Pei-Yuan Cheng,Koping Chang,Hsuan Wang,Jia-Huei Tsai,Jau-Yu Liau,Wen-Chien Chou
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma and is a potentially curable disease. However, it is heterogenous, and the prognosis is poor if the tumor cells harbor fusions involving MYC and BCL2 or MYC and BCL6 (double-hit [DH] lymphoma), or fusions involving all three genes (triple-hit [TH] lymphoma). Fluorescence in situ hybridization is currently the gold
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Post-neoadjuvant assessment of tumour budding according to ITBCC subgroups delivers stage- and regression-grade independent prognostic information in intestinal-type gastric adenocarcinoma. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-06-17 Moritz Jesinghaus,Anna-Lina Herz,Meike Kohlruss,Miguel Silva,Albert Grass,Sebastian Lange,Alexander Novotny,Katja Ott,Thomas Schmidt,Matthias Gaida,Alexander Hapfelmeier,Carsten Denkert,Wilko Weichert,Gisela Keller
Tumour budding (TB) has been associated with adverse clinicopathological factors and poor survival in a plethora of therapy-naïve carcinoma entities including gastric adenocarcinoma (GC). As conventional histopathological grading is usually omitted in the post-neoadjuvant setting of GC, our study aimed to investigate the prognostic impact of TB in GCs resected after neoadjuvant therapy. We evaluated
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Tertiary lymphoid structures favor outcome in resected esophageal squamous cell carcinoma. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-06-16 Rutao Li,Xing Huang,Wenmin Yang,Jifan Wang,Yingkuan Liang,Te Zhang,Qixing Mao,Wenjie Xia,Lin Xu,Xinyu Xu,Gaochao Dong,Feng Jiang
Tertiary lymphoid structures (TLSs) are considered to have a good prognosis in multiple solid tumors. However, the prognostic value of TLS in esophageal squamous cell carcinoma (ESCC) is unknown. In this study, we retrospectively enrolled 185 ESCC patients who underwent surgical resection. Hematoxylin and eosin staining was performed to investigate the presence, the abundance, the maturation, and the
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Assessment of clinical trial protocols for pathology content using the SPIRIT-Path guidelines highlights areas for improvement. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-05-31 Peter Robinson,Chris M Bacon,Shujing J Lim,Abeer M Shaaban,Daniel Brierley,Ian Lewis,David J Harrison,Timothy J Kendall,Max Robinson
The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement provides evidence-based recommendations for the minimum content of clinical trial protocols. The Cellular Molecular Pathology Initiative, hosted by the UK National Cancer Research Institute, developed an extension, SPIRIT-Path, describing how to effectively incorporate pathology support into clinical trial
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Spatial analysis of tumor-infiltrating lymphocytes in histological sections using deep learning techniques predicts survival in colorectal carcinoma. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-04-28 Hongming Xu,Yoon Jin Cha,Jean R Clemenceau,Jinhwan Choi,Sung Hak Lee,Jeonghyun Kang,Tae Hyun Hwang
This study aimed to explore the prognostic impact of spatial distribution of tumor-infiltrating lymphocytes (TILs) quantified by deep learning (DL) approaches based on digitalized whole-slide images stained with hematoxylin and eosin in patients with colorectal cancer (CRC). The prognostic impact of spatial distributions of TILs in patients with CRC was explored in the Yonsei cohort (n = 180) and validated
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Aggressive uveal melanoma displays a high degree of centrosome amplification, opening the door to therapeutic intervention. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-04-26 Dorota Sabat-Pośpiech,Kim Fabian-Kolpanowicz,Helen Kalirai,Natalie Kipling,Sarah E Coupland,Judy M Coulson,Andrew B Fielding
Uveal melanoma (UM) is the most common intraocular cancer in adults. Whilst treatment of primary UM (PUM) is often successful, around 50% of patients develop metastatic disease with poor outcomes, linked to chromosome 3 loss (monosomy 3, M3). Advances in understanding UM cell biology may indicate new therapeutic options. We report that UM exhibits centrosome abnormalities, which in other cancers are
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High cyclin E1 protein, but not gene amplification, is prognostic for basal-like breast cancer. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-04-06 Diar Aziz,Christine Lee,Venessa Chin,Kristine J Fernandez,Zoe Phan,,,Paul Waring,C Elizabeth Caldon
Basal-like breast cancer (BLBC) has a greater overlap in molecular features with high-grade serous ovarian cancer (HGSOC) than with other breast cancer subtypes. Similarities include BRCA1 mutation, high frequency of TP53 mutation, and amplification of CCNE1 (encoding the cyclin E1 protein) in 6-34% of cases, and these features can be used to group patients for targeted therapies in clinical trials
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Homologous recombination deficiency is inversely correlated with microsatellite instability and identifies immunologically cold tumors in most cancer types. J. Pathol. Clin. Res. (IF 4.373) Pub Date : 2022-04-05 Jan Budczies,Klaus Kluck,Susanne Beck,Iordanis Ourailidis,Michael Allgäuer,Michael Menzel,Daniel Kazdal,Lukas Perkhofer,Alexander Kleger,Peter Schirmacher,Thomas Seufferlein,Albrecht Stenzinger
Homologous recombination deficiency (HRD) leads to DNA double-strand breaks and can be exploited by the use of poly (ADP-ribose) polymerase (PARP) inhibitors to induce synthetic lethality. Extending the original therapeutic concept, the role of HRD is currently being investigated in clinical trials testing immune checkpoint blockers alone or in combination with PARP inhibitors, but the relationship