Journal of Pathology Clinical Research最新文献

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A clinically feasible algorithm for the parallel detection of glioma-associated copy number variation markers based on shallow whole genome sequencing 基于浅层全基因组测序平行检测胶质瘤相关拷贝数变异标记的临床可行算法。
IF 3.4 2区 医学
Journal of Pathology Clinical Research Pub Date : 2024-10-07 DOI: 10.1002/2056-4538.70005
Shuai Wu, Chenyu Ma, Jiawei Cai, Chenkang Yang, Xiaojia Liu, Chen Luo, Jingyi Yang, Zhang Xiong, Dandan Cao, Hong Chen
{"title":"A clinically feasible algorithm for the parallel detection of glioma-associated copy number variation markers based on shallow whole genome sequencing","authors":"Shuai Wu,&nbsp;Chenyu Ma,&nbsp;Jiawei Cai,&nbsp;Chenkang Yang,&nbsp;Xiaojia Liu,&nbsp;Chen Luo,&nbsp;Jingyi Yang,&nbsp;Zhang Xiong,&nbsp;Dandan Cao,&nbsp;Hong Chen","doi":"10.1002/2056-4538.70005","DOIUrl":"10.1002/2056-4538.70005","url":null,"abstract":"<p>Molecular features are incorporated into the integrated diagnostic system for adult diffuse gliomas. Of these, copy number variation (CNV) markers, including both arm-level (1p/19q codeletion, +7/−10 signature) and gene-level (<i>EGFR</i> gene amplification, <i>CDKN2A/B</i> homozygous deletion) changes, have revolutionized the diagnostic paradigm by updating the subtyping and grading schemes. Shallow whole genome sequencing (sWGS) has been widely used for CNV detection due to its cost-effectiveness and versatility. However, the parallel detection of glioma-associated CNV markers using sWGS has not been optimized in a clinical setting. Herein, we established a model-based approach to classify the CNV status of glioma-associated diagnostic markers with a single test. To enhance its clinical utility, we carried out hypothesis testing model-based analysis through the estimation of copy ratio fluctuation level, which was implemented individually and independently and, thus, avoided the necessity for normal controls. Besides, the customization of required minimal tumor fraction (TF) was evaluated and recommended for each glioma-associated marker to ensure robust classification. As a result, with 1× sequencing depth and 0.05 TF, arm-level CNVs could be reliably detected with at least 99.5% sensitivity and specificity. For <i>EGFR</i> gene amplification and <i>CDKN2A/B</i> homozygous deletion, the corresponding TF limits were 0.15 and 0.45 to ensure the evaluation metrics were both higher than 97%. Furthermore, we applied the algorithm to an independent glioma cohort and observed the expected sample distribution and prognostic stratification patterns. In conclusion, we provide a clinically applicable algorithm to classify the CNV status of glioma-associated markers in parallel.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deep learning-based analysis of EGFR mutation prevalence in lung adenocarcinoma H&E whole slide images 基于深度学习的肺腺癌 H&E 全切片图像中表皮生长因子受体突变率分析。
IF 3.4 2区 医学
Journal of Pathology Clinical Research Pub Date : 2024-10-02 DOI: 10.1002/2056-4538.70004
Jun Hyeong Park, June Hyuck Lim, Seonhwa Kim, Chul-Ho Kim, Jeong-Seok Choi, Jun Hyeok Lim, Lucia Kim, Jae Won Chang, Dongil Park, Myung-won Lee, Sup Kim, Il-Seok Park, Seung Hoon Han, Eun Shin, Jin Roh, Jaesung Heo
{"title":"Deep learning-based analysis of EGFR mutation prevalence in lung adenocarcinoma H&E whole slide images","authors":"Jun Hyeong Park,&nbsp;June Hyuck Lim,&nbsp;Seonhwa Kim,&nbsp;Chul-Ho Kim,&nbsp;Jeong-Seok Choi,&nbsp;Jun Hyeok Lim,&nbsp;Lucia Kim,&nbsp;Jae Won Chang,&nbsp;Dongil Park,&nbsp;Myung-won Lee,&nbsp;Sup Kim,&nbsp;Il-Seok Park,&nbsp;Seung Hoon Han,&nbsp;Eun Shin,&nbsp;Jin Roh,&nbsp;Jaesung Heo","doi":"10.1002/2056-4538.70004","DOIUrl":"10.1002/2056-4538.70004","url":null,"abstract":"<p><i>EGFR</i> mutations are a major prognostic factor in lung adenocarcinoma. However, current detection methods require sufficient samples and are costly. Deep learning is promising for mutation prediction in histopathological image analysis but has limitations in that it does not sufficiently reflect tumor heterogeneity and lacks interpretability. In this study, we developed a deep learning model to predict the presence of <i>EGFR</i> mutations by analyzing histopathological patterns in whole slide images (WSIs). We also introduced the <i>EGFR</i> mutation prevalence (EMP) score, which quantifies <i>EGFR</i> prevalence in WSIs based on patch-level predictions, and evaluated its interpretability and utility. Our model estimates the probability of EGFR prevalence in each patch by partitioning the WSI based on multiple-instance learning and predicts the presence of <i>EGFR</i> mutations at the slide level. We utilized a patch-masking scheduler training strategy to enable the model to learn various histopathological patterns of EGFR. This study included 868 WSI samples from lung adenocarcinoma patients collected from three medical institutions: Hallym University Medical Center, Inha University Hospital, and Chungnam National University Hospital. For the test dataset, 197 WSIs were collected from Ajou University Medical Center to evaluate the presence of <i>EGFR</i> mutations. Our model demonstrated prediction performance with an area under the receiver operating characteristic curve of 0.7680 (0.7607–0.7720) and an area under the precision-recall curve of 0.8391 (0.8326–0.8430). The EMP score showed Spearman correlation coefficients of 0.4705 (<i>p</i> = 0.0087) for p.L858R and 0.5918 (<i>p</i> = 0.0037) for exon 19 deletions in 64 samples subjected to next-generation sequencing analysis. Additionally, high EMP scores were associated with papillary and acinar patterns (<i>p</i> = 0.0038 and <i>p</i> = 0.0255, respectively), whereas low EMP scores were associated with solid patterns (<i>p</i> = 0.0001). These results validate the reliability of our model and suggest that it can provide crucial information for rapid screening and treatment plans.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring prognostic biomarkers in pathological images of colorectal cancer patients via deep learning 通过深度学习探索结直肠癌患者病理图像中的预后生物标记。
IF 3.4 2区 医学
Journal of Pathology Clinical Research Pub Date : 2024-09-29 DOI: 10.1002/2056-4538.70003
Binshen Wei, Linqing Li, Yenan Feng, Sihan Liu, Peng Fu, Lin Tian
{"title":"Exploring prognostic biomarkers in pathological images of colorectal cancer patients via deep learning","authors":"Binshen Wei,&nbsp;Linqing Li,&nbsp;Yenan Feng,&nbsp;Sihan Liu,&nbsp;Peng Fu,&nbsp;Lin Tian","doi":"10.1002/2056-4538.70003","DOIUrl":"10.1002/2056-4538.70003","url":null,"abstract":"<p>Hematoxylin and eosin (H&amp;E) whole slide images provide valuable information for predicting prognostic outcomes in colorectal cancer (CRC) patients. However, extracting prognostic indicators from pathological images is challenging due to the subtle complexities of phenotypic information. We trained a weakly supervised deep learning model on data from 640 CRC patients in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial dataset and validated it using data from 522 CRC patients in the cancer genome atlas (TCGA) dataset. We created the colorectal cancer risk score (CRCRS) to assess patient prognosis, visualized the pathological phenotype of the risk score using Grad-CAM, and employed multiomics data from the TCGA CRC cohort to investigate the potential biological mechanisms underlying the risk score. The overall survival analysis revealed that the CRCRS served as an independent prognostic indicator for both the PLCO cohort (<i>p</i> &lt; 0.001) and the TCGA cohort (<i>p</i> &lt; 0.001), with its predictive efficacy remaining unaffected by the clinical staging system. Additionally, satisfactory chemotherapeutic benefits were observed in stage II/III CRC patients with high CRCRS but not in those with low CRCRS. A pathomics nomogram constructed by integrating the CRCRS with the tumor-node-metastasis (TNM) staging system enhanced prognostic prediction accuracy compared with using the TNM staging system alone. Noteworthy features of the risk score were identified, such as immature tumor mesenchyme, disorganized gland structures, small clusters of cancer cells associated with unfavorable prognosis, and infiltrating inflammatory cells associated with favorable prognosis. The TCGA multiomics data revealed potential correlations between the CRCRS and the activation of energy production and metabolic pathways, the tumor immune microenvironment, and genetic mutations in <i>APC</i>, <i>SMAD2</i>, <i>EEF1AKMT4</i>, <i>EPG5</i>, and <i>TANC1</i>. In summary, our deep learning algorithm identified the CRCRS as a prognostic indicator in CRC, providing a significant approach for prognostic risk stratification and tailoring precise treatment strategies for individual patients.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142356370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Validation of a whole slide image management system for metabolic-associated steatohepatitis for clinical trials 验证用于临床试验的代谢相关性脂肪性肝炎全切片图像管理系统。
IF 3.4 2区 医学
Journal of Pathology Clinical Research Pub Date : 2024-09-18 DOI: 10.1002/2056-4538.12395
Hanna Pulaski, Shraddha S Mehta, Laryssa C Manigat, Stephanie Kaufman, Hypatia Hou, ILKe Nalbantoglu, Xuchen Zhang, Emily Curl, Ross Taliano, Tae Hun Kim, Michael Torbenson, Jonathan N Glickman, Murray B Resnick, Neel Patel, Cristin E Taylor, Pierre Bedossa, Michael C Montalto, Andrew H Beck, Katy E Wack
{"title":"Validation of a whole slide image management system for metabolic-associated steatohepatitis for clinical trials","authors":"Hanna Pulaski,&nbsp;Shraddha S Mehta,&nbsp;Laryssa C Manigat,&nbsp;Stephanie Kaufman,&nbsp;Hypatia Hou,&nbsp;ILKe Nalbantoglu,&nbsp;Xuchen Zhang,&nbsp;Emily Curl,&nbsp;Ross Taliano,&nbsp;Tae Hun Kim,&nbsp;Michael Torbenson,&nbsp;Jonathan N Glickman,&nbsp;Murray B Resnick,&nbsp;Neel Patel,&nbsp;Cristin E Taylor,&nbsp;Pierre Bedossa,&nbsp;Michael C Montalto,&nbsp;Andrew H Beck,&nbsp;Katy E Wack","doi":"10.1002/2056-4538.12395","DOIUrl":"10.1002/2056-4538.12395","url":null,"abstract":"<p>The gold standard for enrollment and endpoint assessment in metabolic dysfunction-associated steatosis clinical trials is histologic assessment of a liver biopsy performed on glass slides. However, obtaining the evaluations from several expert pathologists on glass is challenging, as shipping the slides around the country or around the world is time-consuming and comes with the hazards of slide breakage. This study demonstrated that pathologic assessment of disease activity in steatohepatitis, performed using digital images on the AISight whole slide image management system, yields results that are comparable to those obtained using glass slides. The accuracy of scoring for steatohepatitis (nonalcoholic fatty liver disease activity score ≥4 with ≥1 for each feature and absence of atypical features suggestive of other liver disease) performed on the system was evaluated against scoring conducted on glass slides. Both methods were assessed for overall percent agreement with a consensus “ground truth” score (defined as the median score of a panel of three pathologists’ glass slides). Each case was also read by three different pathologists, once on glass and once digitally with a minimum 2-week washout period between the modalities. It was demonstrated that the average agreement across three pathologists of digital scoring with ground truth was noninferior to the average agreement of glass scoring with ground truth [noninferiority margin: −0.05; difference: −0.001; 95% CI: (−0.027, 0.026); and <i>p</i> &lt; 0.0001]. For each pathologist, there was a similar average agreement of digital and glass reads with glass ground truth (pathologist A, 0.843 and 0.849; pathologist B, 0.633 and 0.605; and pathologist C, 0.755 and 0.780). Here, we demonstrate that the accuracy of digital reads for steatohepatitis using digital images is equivalent to glass reads in the context of a clinical trial for scoring using the Clinical Research Network scoring system.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.12395","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Challenges for pathologists in implementing clinical microbiome diagnostic testing 病理学家在实施临床微生物组诊断检测时面临的挑战
IF 3.4 2区 医学
Journal of Pathology Clinical Research Pub Date : 2024-09-17 DOI: 10.1002/2056-4538.70002
Yulia Gerasimova, Haroon Ali, Urooba Nadeem
{"title":"Challenges for pathologists in implementing clinical microbiome diagnostic testing","authors":"Yulia Gerasimova,&nbsp;Haroon Ali,&nbsp;Urooba Nadeem","doi":"10.1002/2056-4538.70002","DOIUrl":"https://doi.org/10.1002/2056-4538.70002","url":null,"abstract":"<p>Recent research has established that the microbiome plays potential roles in the pathogenesis of numerous chronic diseases, including carcinomas. This discovery has led to significant interest in clinical microbiome testing among physicians, translational investigators, and the lay public. As novel, inexpensive methodologies to interrogate the microbiota become available, research labs and commercial vendors have offered microbial assays. However, these tests still have not infiltrated the clinical laboratory space. Here, we provide an overview of the challenges of implementing microbiome testing in clinical pathology. We discuss challenges associated with preanalytical and analytic sample handling and collection that can influence results, choosing the appropriate testing methodology for the clinical context, establishing reference ranges, interpreting the data generated by testing and its value in making patient care decisions, regulation, and cost considerations of testing. Additionally, we suggest potential solutions for these problems to expedite the establishment of microbiome testing in the clinical laboratory.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The expression of YAP1 and other transcription factors contributes to lineage plasticity in combined small cell lung carcinoma YAP1和其他转录因子的表达促进了合并小细胞肺癌的细胞系可塑性
IF 3.4 2区 医学
Journal of Pathology Clinical Research Pub Date : 2024-09-16 DOI: 10.1002/2056-4538.70001
Naoe Jimbo, Chiho Ohbayashi, Tomomi Fujii, Maiko Takeda, Suguru Mitsui, Yugo Tanaka, Tomoo Itoh, Yoshimasa Maniwa
{"title":"The expression of YAP1 and other transcription factors contributes to lineage plasticity in combined small cell lung carcinoma","authors":"Naoe Jimbo,&nbsp;Chiho Ohbayashi,&nbsp;Tomomi Fujii,&nbsp;Maiko Takeda,&nbsp;Suguru Mitsui,&nbsp;Yugo Tanaka,&nbsp;Tomoo Itoh,&nbsp;Yoshimasa Maniwa","doi":"10.1002/2056-4538.70001","DOIUrl":"https://doi.org/10.1002/2056-4538.70001","url":null,"abstract":"<p>Lineage plasticity in small cell lung carcinoma (SCLC) causes therapeutic difficulties. This study aimed to investigate the pathological findings of plasticity in SCLC, focusing on combined SCLC, and elucidate the involvement of YAP1 and other transcription factors. We analysed 100 surgically resected SCLCs through detailed morphological observations and immunohistochemistry for YAP1 and other transcription factors. Component-by-component next-generation sequencing (<i>n</i> = 15 pairs) and immunohistochemistry (<i>n</i> = 35 pairs) were performed on the combined SCLCs. Compared with pure SCLCs (<i>n</i> = 65), combined SCLCs (<i>n</i> = 35) showed a significantly larger size, higher expression of NEUROD1, and higher frequency of double-positive transcription factors (<i>p</i> = 0.0009, 0.04, and 0.019, respectively). Notably, 34% of the combined SCLCs showed morphological mosaic patterns with unclear boundaries between the SCLC and its partner. Combined SCLCs not only had unique histotypes as partners but also represented different lineage plasticity within the partner. NEUROD1-dominant combined SCLCs had a significantly higher proportion of adenocarcinomas as partners, whereas POU2F3-dominant combined SCLCs had a significantly higher proportion of squamous cell carcinomas as partners (<i>p</i> = 0.006 and <i>p</i> = 0.0006, respectively). YAP1 expression in SCLC components was found in 80% of combined SCLCs and 62% of pure SCLCs, often showing mosaic-like expression. Among the combined SCLCs with component-specific analysis, the identical <i>TP53</i> mutation was found in 10 pairs, and the identical <i>Rb1</i> abnormality was found in 2 pairs. On immunohistochemistry, the same abnormal p53 pattern was found in 34 pairs, and Rb1 loss was found in 24 pairs. In conclusion, combined SCLC shows a variety of pathological plasticity. Although combined SCLC is more plastic than pure SCLC, pure SCLC is also a phenotypically plastic tumour. The morphological mosaic pattern and YAP1 mosaic-like expression may represent ongoing lineage plasticity. This study also identified the relationship between transcription factors and partners in combined SCLC. Transcription factors may be involved in differentiating specific cell lineages beyond just ‘neuroendocrine’.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TROP2 in colorectal carcinoma: associations with histopathology, molecular phenotype, and patient prognosis 结直肠癌中的 TROP2:与组织病理学、分子表型和患者预后的关系。
IF 3.4 2区 医学
Journal of Pathology Clinical Research Pub Date : 2024-08-23 DOI: 10.1002/2056-4538.12394
Sebastian Foersch, Maxime Schmitt, Anne-Sophie Litmeyer, Markus Tschurtschenthaler, Thomas Gress, Detlef K Bartsch, Nicole Pfarr, Katja Steiger, Carsten Denkert, Moritz Jesinghaus
{"title":"TROP2 in colorectal carcinoma: associations with histopathology, molecular phenotype, and patient prognosis","authors":"Sebastian Foersch,&nbsp;Maxime Schmitt,&nbsp;Anne-Sophie Litmeyer,&nbsp;Markus Tschurtschenthaler,&nbsp;Thomas Gress,&nbsp;Detlef K Bartsch,&nbsp;Nicole Pfarr,&nbsp;Katja Steiger,&nbsp;Carsten Denkert,&nbsp;Moritz Jesinghaus","doi":"10.1002/2056-4538.12394","DOIUrl":"10.1002/2056-4538.12394","url":null,"abstract":"<p>Antibody–drug conjugates (ADCs) directed to trophoblast cell surface antigen 2 (TROP2) have gained approval as a therapeutic option for advanced triple-negative breast cancer, and TROP2 expression has been linked to unfavourable outcomes in various malignancies. In colorectal carcinoma (CRC), there is still a lack of comprehensive studies on its expression frequency and its prognostic implications in relation to the main clinicopathological parameters. We examined the expression of TROP2 in a large cohort of 1,052 CRC cases and correlated our findings with histopathological and molecular parameters, tumour stage, and patient outcomes. TROP2 was heterogeneously expressed in 214/1,052 CRCs (20.3%), with only a fraction of strongly positive tumours. TROP2 expression significantly correlated with an invasive histological phenotype (e.g. increased tumour budding/aggressive histopathological subtypes), advanced tumour stage, microsatellite stable tumours, and p53 alterations. While TROP2 expression was prognostic in univariable analyses of the overall cohort (e.g. for disease-free survival, <i>p</i> &lt; 0.001), it exhibited distinct variations among important clinicopathological subgroups (e.g. right- versus left-sided CRC, microsatellite stable versus unstable CRC, Union for International Cancer Control [UICC] stages) and lost its significance in multivariable analyses that included stage and CRC histopathology. In summary, TROP2 is quite frequently expressed in CRC and associated with an aggressive histopathological phenotype and microsatellite stable tumours. Future clinical trials investigating anti-TROP2 ADCs should acknowledge the observed intratumoural heterogeneity, given that only a subset of TROP2-expressing CRC show strong positivity. The prognostic implications of TROP2 are complex and show substantial variations across crucial clinicopathological subgroups, thus indicating that TROP2 is a suboptimal parameter to predict patient prognosis.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.12394","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Predicting lymph node recurrence in cT1-2N0 tongue squamous cell carcinoma: collaboration between artificial intelligence and pathologists 预测 cT1-2N0 舌鳞状细胞癌的淋巴结复发:人工智能与病理学家的合作。
IF 3.4 2区 医学
Journal of Pathology Clinical Research Pub Date : 2024-08-19 DOI: 10.1002/2056-4538.12392
Masahiro Adachi, Tetsuro Taki, Motohiro Kojima, Naoya Sakamoto, Kazuto Matsuura, Ryuichi Hayashi, Keiji Tabuchi, Shumpei Ishikawa, Genichiro Ishii, Shingo Sakashita
{"title":"Predicting lymph node recurrence in cT1-2N0 tongue squamous cell carcinoma: collaboration between artificial intelligence and pathologists","authors":"Masahiro Adachi,&nbsp;Tetsuro Taki,&nbsp;Motohiro Kojima,&nbsp;Naoya Sakamoto,&nbsp;Kazuto Matsuura,&nbsp;Ryuichi Hayashi,&nbsp;Keiji Tabuchi,&nbsp;Shumpei Ishikawa,&nbsp;Genichiro Ishii,&nbsp;Shingo Sakashita","doi":"10.1002/2056-4538.12392","DOIUrl":"10.1002/2056-4538.12392","url":null,"abstract":"<p>Researchers have attempted to identify the factors involved in lymph node recurrence in cT1-2N0 tongue squamous cell carcinoma (SCC). However, studies combining histopathological and clinicopathological information in prediction models are limited. We aimed to develop a highly accurate lymph node recurrence prediction model for clinical stage T1-2, N0 (cT1-2N0) tongue SCC by integrating histopathological artificial intelligence (AI) with clinicopathological information. A dataset from 148 patients with cT1-2N0 tongue SCC was divided into training and test sets. The prediction models were constructed using AI-extracted information from whole slide images (WSIs), human-assessed clinicopathological information, and both combined. Weakly supervised learning and machine learning algorithms were used for WSIs and clinicopathological information, respectively. The combination model utilised both algorithms. Highly predictive patches from the model were analysed for histopathological features. In the test set, the areas under the receiver operating characteristic (ROC) curve for the model using WSI, clinicopathological information, and both combined were 0.826, 0.835, and 0.991, respectively. The highest area under the ROC curve was achieved with the model combining WSI and clinicopathological factors. Histopathological feature analysis showed that highly predicted patches extracted from recurrence cases exhibited significantly more tumour cells, inflammatory cells, and muscle content compared with non-recurrence cases. Moreover, patches with mixed inflammatory cells, tumour cells, and muscle were significantly more prevalent in recurrence versus non-recurrence cases. The model integrating AI-extracted histopathological and human-assessed clinicopathological information demonstrated high accuracy in predicting lymph node recurrence in patients with cT1-2N0 tongue SCC.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.12392","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
VEGFA gene variants are associated with breast cancer progression VEGFA 基因变异与乳腺癌进展有关。
IF 3.4 2区 医学
Journal of Pathology Clinical Research Pub Date : 2024-08-09 DOI: 10.1002/2056-4538.12393
Jessica Furriol, Elisabeth Wik, Sura Aziz, Cecilie Askeland, Gøril Knutsvik, Lars A Akslen
{"title":"VEGFA gene variants are associated with breast cancer progression","authors":"Jessica Furriol,&nbsp;Elisabeth Wik,&nbsp;Sura Aziz,&nbsp;Cecilie Askeland,&nbsp;Gøril Knutsvik,&nbsp;Lars A Akslen","doi":"10.1002/2056-4538.12393","DOIUrl":"10.1002/2056-4538.12393","url":null,"abstract":"<p>Angiogenesis is recognized as a hallmark of cancer, and vascular endothelial growth factor (VEGF) is a key regulator of the angiogenic process and is related to cancer progression. Anti-VEGF therapy has been tried but with limited success and without useful stratification for angiogenesis markers. Further, the landscape of VEGF single nucleotide polymorphisms (SNPs) in breast cancer and their clinical relevance is not well studied, and their relation to tissue-based angiogenesis markers has not been explored. Here, we studied a selection of VEGFA SNPs in nontumor lymph nodes from a population-based breast cancer cohort (<i>n</i> = 544), and their relation to clinicopathologic variables, vascular tissue metrics, and breast cancer-specific survival. Two of the SNP candidates (rs833068GA genotype and rs25648CC genotype) showed associations with angiogenesis tissue markers, and the VEGFA rs833068GA genotype was associated with breast cancer-specific survival among ER-negative cases. We also found trends of association between the rs699947CA genotype and large tumor diameter and ER-negative tumors, and between the rs3025039CC genotype and large tumor diameter. Our findings indicate some associations between certain VEGF SNPs, in particular the rs833068GA genotype, and both vascular metrics and patient survival. These findings and their potential implications need to be validated by independent studies.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Homologous recombination deficiency (HRD) is associated with better prognosis and possibly causes a non-inflamed tumour microenvironment in nasopharyngeal carcinoma 同源重组缺陷(HRD)与较好的预后有关,并可能导致鼻咽癌的肿瘤微环境不发炎。
IF 3.4 2区 医学
Journal of Pathology Clinical Research Pub Date : 2024-08-05 DOI: 10.1002/2056-4538.12391
Xinyi Zhou, Haoxuan Ying, Yujie Sun, Wenda Zhang, Peng Luo, Shuhan Zhu, Jian Zhang
{"title":"Homologous recombination deficiency (HRD) is associated with better prognosis and possibly causes a non-inflamed tumour microenvironment in nasopharyngeal carcinoma","authors":"Xinyi Zhou,&nbsp;Haoxuan Ying,&nbsp;Yujie Sun,&nbsp;Wenda Zhang,&nbsp;Peng Luo,&nbsp;Shuhan Zhu,&nbsp;Jian Zhang","doi":"10.1002/2056-4538.12391","DOIUrl":"10.1002/2056-4538.12391","url":null,"abstract":"<p>Homologous recombination deficiency (HRD) score is a reliable indicator of genomic instability. The significance of HRD in nasopharyngeal carcinoma (NPC), particularly its influence on prognosis and the immune microenvironment, has yet to be adequately explored. Understanding HRD status comprehensively can offer valuable insights for guiding precision treatment. We utilised three cohorts to investigate HRD status in NPC: the Zhujiang cohort from local collection and the Hong Kong (SRA288429) and Singapore (SRP035573) cohorts from public datasets. The GATK (genome analysis toolkit) best practice process was employed to investigate germline and somatic <i>BRCA1/2</i> mutations and various bioinformatics tools and algorithms to examine the association between HRD status and clinical molecular characteristics. We found that individuals with a negative HRD status (no-HRD) exhibited a higher risk of recurrence [hazard ratio (HR), 1.43; 95% confidence interval (CI), 2.03–333.76; <i>p</i> = 0.012] in the Zhujiang cohort, whereas, in the Singapore cohort, they experienced a higher risk of mortality (HR, 26.04; 95% CI, 1.43–34.21; <i>p</i> = 0.016) compared with those in the HRD group. <i>In vitro</i> experiments demonstrated that NPC cells with BRCA1 knockdown exhibit heightened sensitivity to chemoradiotherapy. Furthermore, the HRD group showed significantly higher tumour mutational burden and tumour neoantigen burden levels than the no-HRD group. Immune infiltration analysis indicated that HRD tissues tend to have a non-inflamed tumour microenvironment. In conclusion, patients with HRD exhibit a comparatively favourable prognosis in NPC, possibly associated with a non-inflammatory immune microenvironment. These findings have positive implications for treatment stratification, enabling the selection of more precise and effective therapeutic approaches and aiding in the prediction of treatment response and prognosis to a certain extent.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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