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JOURNAL ARTICLE
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 parietal and neuroendocrine cells in the oxyntic mucosa, and sparing of the antral mucosa. The patients were found to harbor pathogenic variants in telomeropathic genes (POT1 and DCLRE1B)...
November 22, 2023: Journal of Pathology. Clinical Research
#22
JOURNAL ARTICLE
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 Hamed, Zsolt Lázár, Zsolt Pauker, Gáspár Radványi, Adrienn Kiss, Gábor Körösmezey, János Jakucs, Péter J Dombi, Zsófia Simon, Zsolt Klucsik, Mihály Gurzó, Márta Tiboly, Tímea Vidra, Péter Ilonczai, András Bors, Hajnalka Andrikovics, Miklós Egyed, Tamás Székely, András Masszi, Donát Alpár, András Matolcsy, Csaba Bödör
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 study, we aimed to scrutinise the subclonal architecture and clinical impact of TP53 mutations using a sensitive, NGS-based mutation analysis in a 'real-world' cohort of 901 patients with CLL...
November 21, 2023: Journal of Pathology. Clinical Research
#23
JOURNAL ARTICLE
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 to find survival differences. All tumors in this study were negative for Epstein-Barr virus-encoded small RNAs (EBERs) and almost all showed no loss of mismatch repair (MMR) proteins and were positive for alpha fetoprotein (AFP or spalt like transcription factor 4 (SALL4)...
November 16, 2023: Journal of Pathology. Clinical Research
#24
JOURNAL ARTICLE
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) inhibitor treatment. We evaluated KDM5D copy number loss in 173 surgically resected SCCs from male patients using fluorescence in situ hybridization...
November 16, 2023: Journal of Pathology. Clinical Research
#25
JOURNAL ARTICLE
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 datasets that are attractive for automated computational analysis, there is also a desire to use 3D pathology to improve the visual assessment of tissue histology...
November 2, 2023: Journal of Pathology. Clinical Research
#26
EDITORIAL
Kamran Abbasi, Parveen Ali, Virginia Barbour, Kirsten Bibbins-Domingo, Marcel Gm Olde Rikkert, Andy Haines, Ira Helfand, Richard Horton, Bob Mash, Arun Mitra, Carlos Monteiro, Elena N Naumova, Eric J Rubin, Tilman Ruff, Peush Sahni, James Tumwine, Paul Yonga, Chris Zielinski
No abstract text is available yet for this article.
November 2023: Journal of Pathology. Clinical Research
#27
JOURNAL ARTICLE
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 metastases. Cellular features, including tumor nuclei morphological and graph features as well as cytoplasm texture features, were extracted by computer algorithms from 175 slides (114 patients)...
October 11, 2023: Journal of Pathology. Clinical Research
#28
JOURNAL ARTICLE
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 mucin-domain containing-3 (TIM-3) and B7 homolog 3 protein (B7-H3) in 58 GEA and investigated their prognostic significance as well as association with PD-L1 expression and other known prognostic factors...
October 5, 2023: Journal of Pathology. Clinical Research
#29
JOURNAL ARTICLE
Anja L Frei, Anthony McGuigan, Ritik Rak Sinha, Mark A Glaire, Faiz Jabbar, Luciana Gneo, Tijana Tomasevic, Andrea Harkin, Tim J Iveson, Mark Saunders, Karin Oein, Noori Maka, Francesco Pezella, Leticia Campo, Jennifer Hay, Joanne Edwards, Owen J Sansom, Caroline Kelly, Ian Tomlinson, Wanja Kildal, Rachel S Kerr, David J Kerr, Håvard E Danielsen, Enric Domingo, David N Church, Viktor H Koelzer
Multiplex immunofluorescence (mIF) imaging can provide comprehensive quantitative and spatial information for multiple immune markers for tumour immunoprofiling. However, application at scale to clinical trial samples sourced from multiple institutions is challenging due to pre-analytical heterogeneity. This study reports an analytical approach to the largest multi-parameter immunoprofiling study of clinical trial samples to date. We analysed 12,592 tissue microarray (TMA) spots from 3,545 colorectal cancers sourced from more than 240 institutions in two clinical trials (QUASAR 2 and SCOT) stained for CD4, CD8, CD20, CD68, FoxP3, pan-cytokeratin, and DAPI by mIF...
September 11, 2023: Journal of Pathology. Clinical Research
#30
JOURNAL ARTICLE
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 digitally segmented whole slide image. We compared the clinical presentations, radiological features, and prognoses of the different clusters...
September 4, 2023: Journal of Pathology. Clinical Research
#31
JOURNAL ARTICLE
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 large cohort of conventional CRCs and MANECs/NECs. In conventional CRC, we put a special focus on conventional CRC with diffuse expression of synaptophysin, which carry the risk of being misinterpreted as a MANEC or a NEC...
August 22, 2023: Journal of Pathology. Clinical Research
#32
JOURNAL ARTICLE
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 biomarker for NT prognosis. A TERT break-apart probe for fluorescence in situ hybridisation (FISH) was designed, optimised, and applied to assess the genomic status of TERT in Chinese children with NTs at the Beijing Children's Hospital from 2016 to 2019...
August 22, 2023: Journal of Pathology. Clinical Research
#33
JOURNAL ARTICLE
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 basis of these giant cell-rich tumours is unclear and DNA methylation profiling has been shown to be clinically useful for the diagnosis of other tumour types...
August 9, 2023: Journal of Pathology. Clinical Research
#34
JOURNAL ARTICLE
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 serous ovarian carcinoma (HGSOC) samples in four European laboratories. Here, we confirm that subtle differences in staining procedures result in low variability of RAD51 and γH2AX scores...
July 28, 2023: Journal of Pathology. Clinical Research
#35
JOURNAL ARTICLE
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 identified recurrent mutations in epigenetic modifiers, notably KMT2C, ARID1A, NSD1, and KMT2D, in 61.11% of cases...
July 3, 2023: Journal of Pathology. Clinical Research
#36
JOURNAL ARTICLE
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 cohort to analyze the biological function and clinical significance of GFPT2. The correlation of GFPT2 with immune cells and stromal cells was analyzed in the GC immune microenvironment through transcriptome sequencing data and a public single-cell sequencing database...
July 3, 2023: Journal of Pathology. Clinical Research
#37
JOURNAL ARTICLE
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 of follow-up. Somatic activating KRAS codon 12 mutations were detected in endometriosis lesions using droplet digital PCR...
July 2023: Journal of Pathology. Clinical Research
#38
JOURNAL ARTICLE
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 tools such as TIMER, GEPIA, HPA, and UALCAN, we predicted ANXA9 expression and its correlation with the clinicopathological characteristics of BCA patients...
June 9, 2023: Journal of Pathology. Clinical Research
#39
JOURNAL ARTICLE
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 show distinctive recurrence patterns and post-operative survival outcomes. To test this hypothesis, we utilised a multi-institutional cohort of 1,146 resected pancreatic carcinomas and assessed KRAS mutations by droplet digital polymerase chain reaction and CDKN2A, p53, and SMAD4 expression by immunohistochemistry...
June 8, 2023: Journal of Pathology. Clinical Research
#40
JOURNAL ARTICLE
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 DM status and dual epigenetic changes was evaluated in PDAC specimens from patients who underwent radical surgical resection...
May 28, 2023: Journal of Pathology. Clinical Research
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