Journal of Pathology Clinical Research最新文献

{"title":"Association between individual Warburg-related proteins and prognosis in colorectal cancer","authors":"Kelly Offermans,&nbsp;Josien CA Jenniskens,&nbsp;Colinda CJM Simons,&nbsp;Iryna Samarska,&nbsp;Gregorio E Fazzi,&nbsp;Kim M Smits,&nbsp;Leo J Schouten,&nbsp;Matty P Weijenberg,&nbsp;Heike I Grabsch,&nbsp;Piet A van den Brandt","doi":"10.1002/2056-4538.70016","DOIUrl":"https://doi.org/10.1002/2056-4538.70016","url":null,"abstract":"<p>We previously showed that Warburg subtyping (low/moderate/high), based on the expression of six glycolytic proteins and transcriptional regulators [glucose transporter 1 (GLUT1), pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA), monocarboxylate transporter 4 (MCT4), p53, and PTEN], holds independent prognostic value in colorectal cancer (CRC) patients. The present study aimed to investigate whether the expression level of one of the proteins (GLUT1, PKM2, LDHA, MCT4, p53, and PTEN) can act as a proxy for our previously identified six protein-based Warburg subtypes. Protein expression levels for individual Warburg-related proteins were available for 2,251 CRC patients from the Netherlands Cohort Study. Kaplan–Meier curves and Cox regression were used to explore associations between individual Warburg-related proteins and CRC-specific and overall survival. Previously identified associations between Warburg subtypes and CRC-specific and overall survival were adjusted for individual proteins, showing a significant association with survival in the current study. Multivariable-adjusted analyses showed that the expression of GLUT1, LDHA, MCT4, PKM2, or p53 was associated with neither CRC-specific nor overall survival. Decreasing PTEN expression was associated with significantly poorer overall survival (<i>p-</i>trend_categories = 0.026). Additional adjustment for PTEN expression had minimal impact on the previously identified association between Warburg subtypes and survival, and the six protein-based Warburg-high subtype remained a statistically significant predictor of overall survival (hazard ratio 1.15; 95% CI 1.01–1.32). In conclusion, our results emphasise that individual Warburg-related proteins cannot serve as a proxy or surrogate marker for Warburg subtyping, thereby highlighting the importance of combining the expression levels of multiple Warburg-related proteins when examining the prognostic significance of a complex biological pathway such as the Warburg effect.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513479","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}

{"title":"Comprehensive transcriptomic profiling reveals molecular characteristics and biomarkers associated with risk stratification in papillary thyroid carcinoma","authors":"Congcong Yan,&nbsp;Chen Zheng,&nbsp;Jiaxing Luo,&nbsp;Xue Wu,&nbsp;Xinyu Meng,&nbsp;Chaoyue Lv,&nbsp;Shurong Shen,&nbsp;Meng Zhou,&nbsp;Ouchen Wang","doi":"10.1002/2056-4538.70022","DOIUrl":"https://doi.org/10.1002/2056-4538.70022","url":null,"abstract":"<p>Papillary thyroid carcinoma (PTC) is one of the most common endocrine malignancies, with varying levels of risk and clinical behavior. A better understanding of the molecular characteristics could improve molecular diagnosis and risk assessment. In this study, we performed whole transcriptomic sequencing on 113 PTC cases, including 70 high-risk and 43 low-risk Chinese patients. Comparative transcriptional profiling analysis revealed two functionally distinct patterns of gene dysregulation between the risk subtypes. Low-risk PTCs showed significant upregulation of immune-related genes and increased immune cell infiltration, whereas high-risk PTCs presented extensive alterations in gene expression and activation of oncogenic signaling pathways. Additionally, we developed a 31-gene transcriptomic signature (PTCrisk) for differentiating high-risk from low-risk PTCs, which was validated across both in-house and external multicenter cohorts. PTCrisk scores were positively correlated with key clinicopathological features, including tumor size, lymph node metastasis, TNM stage, and <i>BRAF</i> mutation status. Overall, our study provides further molecular insights into PTC risk stratification and may contribute to the development of personalized therapeutic strategies for PTC patients.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489789","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}

{"title":"Subtype-associated complexity and prognostic significance of the NLRP3 inflammasome landscape in pancreatic neoplasms","authors":"Kristóf Németh,&nbsp;Eszter Mezei,&nbsp;Justína Vörös,&nbsp;Katalin Borka,&nbsp;Adrián Pesti,&nbsp;István Kenessey,&nbsp;András Kiss,&nbsp;András Budai","doi":"10.1002/2056-4538.70019","DOIUrl":"https://doi.org/10.1002/2056-4538.70019","url":null,"abstract":"<p>Intraductal papillary mucinous neoplasm (IPMN) can progress into malignant pancreatic cancer, posing challenges in accurately assessing the risk of malignancy. While the nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) inflammasome pathway's role in pancreatic ductal adenocarcinoma (PDAC) has been extensively studied, its implications in IPMN remain unexplored. This study aimed to investigate the prognostic significance of NLRP3 inflammasome-related proteins across IPMN subtypes and their associations with tumor characteristics, with a secondary focus on comparing expression patterns in IPMN and PDAC. A cohort of 187 patients (100 IPMN and 87 PDAC) underwent high-dimensional histopathological imaging using the multiplexed immunohistochemical consecutive staining on single slide method and a semi-automated image analysis workflow. Expression levels of NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), caspase-1, interleukin-1 beta, interleukin-18 (IL-18), interleukin-1 receptor antagonist, and interleukin-18 binding protein (IL-18BP) were evaluated and compared between IPMN and PDAC samples. The relationships between protein expression and tumor characteristics were examined. Principal component analysis distinguished between intestinal and nonintestinal clusters based on NLRP3-associated proteins. Lower IL-18 expression was linked to the intestinal subtype, while higher caspase-1 was linked to the pancreatobiliary subtype. Elevated caspase-1 and ASC expression were associated with invasiveness in IPMN. No significant correlation was found between the examined proteins and later-stage tumor characteristics in invasive cases. The IL-18/IL-18BP ratio was an independent prognostic factor in invasive IPMN. Our findings highlight the prognostic significance of IL-18 and the IL-18/IL-18BP ratio in invasive IPMNs. These results point to a complex regulation of NLRP3 inflammasome proteins, especially effector cytokines, in pancreatic neoplasms, which are strongly linked to subtype and prognosis.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447109","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}

{"title":"Sarcomatoid areas of urothelial carcinoma are enriched for CD163-positive antigen-presenting cells","authors":"Burles A Johnson III,&nbsp;Vamsi Parimi,&nbsp;Sonia Kamanda,&nbsp;David C Corney,&nbsp;Woonyoung Choi,&nbsp;Jean Hoffman-Censits,&nbsp;Max Kates,&nbsp;David J McConkey,&nbsp;Noah M Hahn,&nbsp;Andres Matoso","doi":"10.1002/2056-4538.70021","DOIUrl":"https://doi.org/10.1002/2056-4538.70021","url":null,"abstract":"<p>Sarcomatoid urothelial carcinoma (SUC) is a rare histologic subtype with poor prognosis. While there is known intra-tumoral heterogeneity between individual SUC tumors, the relationship between sarcomatoid and conventional urothelial carcinoma (CUC) within the same patient is poorly understood. The objective of this study was to identify differences between the sarcomatoid and CUC tumor microenvironment components that may drive this aggressive phenotype. Using tissue microarrays from eight patient tumors with mixed CUC and SUC, we examined paired CUC, mixed urothelial carcinoma (UC) regions, and SUC using the Nanostring Digital Spatial Profiling platform. We found SUC and mixed UC had higher levels of stromal cells, predominately macrophages and fibroblasts, when compared with CUC within the same tumor. CD14, CD163, and transforming growth factor-beta levels were significantly higher in SUC than in CUC. Immunohistochemical analysis revealed consistently moderate to strong expression of CD163-positive antigen-presenting cells (APCs) in SUC regions, whereas CD68-positive APC expression was generally absent. Thus, in mixed histology SUC, the SUC component preferentially expressed CD163-positive APCs and fibroblasts compared to the CUC component. As CD163-positive APCs and fibroblasts are known to be tumor-promoting and immune-suppressive, this infiltration may contribute to epithelial to mesenchymal transition and other aggressive properties of SUC.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447112","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}

{"title":"Platinum drugs upregulate CXCR4 and PD-L1 expression via ROS-dependent pathways, with implications for novel combined treatment in gastric cancer","authors":"Xiaoyu Kang,&nbsp;Lin Zhang,&nbsp;Shushang Liu,&nbsp;Fei Wang,&nbsp;Haiming Liu,&nbsp;Fenli Zhou,&nbsp;Fei Wu,&nbsp;Haohao Zhang,&nbsp;Daiming Fan,&nbsp;Yongzhan Nie,&nbsp;Zhangqian Chen","doi":"10.1002/2056-4538.70015","DOIUrl":"10.1002/2056-4538.70015","url":null,"abstract":"<p>CXC chemokine receptor 4 (CXCR4) and programmed cell death-ligand 1 (PD-L1) are two critical molecules involved in the tumor immune microenvironment. However, the impact of platinum drugs, such as cisplatin, on CXCR4 or PD-L1 expression and the underlying mechanisms in gastric cancer (GC) remain unknown. Moreover, the correlation between their expression levels in GC remains elusive. Immunohistochemistry, western blot, and RT-qPCR were performed to determine the expression pattern of CXCR4 and PD-L1 in GC. Clinical samples, patient-derived xenografts, and cell-derived xenografts were utilized to investigate the effects of platinum drugs on the expression levels of CXCR4 and PD-L1. Postchemotherapy resected GC tumor tissues showed higher CXCR4 and PD-L1 expression levels than pretreatment biopsies (<i>p</i> &lt; 0.05). Similarly, GC xenografts treated with platinum-based chemotherapy exhibited increased CXCR4 and PD-L1 expression levels compared to saline-treated controls (<i>p</i> &lt; 0.05). A positive correlation was detected between the expression levels of CXCR4 and PD-L1 in GC tumor tissues. Increased levels of CXCR4 and PD-L1 expression, in a dose- and time-dependent manner upon cisplatin treatment, were observed in GC cells (<i>p</i> &lt; 0.05). Cisplatin-induced CXCR4 upregulation relies on ROS/HIF-1α and ROS/NF-κB pathways, while cisplatin-induced PD-L1 upregulation is cyclic GMP-AMP synthase/stimulator of IFN genes-dependent and associated with elevated ROS levels in GC cells. CXCR4 expression was found to be positively correlated with PD-L1 expression in GC. Platinum drugs upregulated the levels of CXCR4 and PD-L1 expression in GC. A combined strategy targeting CXCR-4 and PD-L1 might have clinical prospects for GC patients.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053834","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}

{"title":"Authors' reply: Re: Koga et al. Retrieval-augmented generation versus document-grounded generation: a key distinction in large language models","authors":"Katherine J Hewitt,&nbsp;Isabella C Wiest,&nbsp;Jakob N Kather","doi":"10.1002/2056-4538.70013","DOIUrl":"10.1002/2056-4538.70013","url":null,"abstract":"&lt;p&gt;We thank Koga &lt;i&gt;et al&lt;/i&gt; for their knowledgeable comments on our work. Their letter highlights a valid question that requires clarification [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Our study assessed the ability of three large language models (LLMs) to diagnose neuropathology cases from free-text descriptions of adult-type diffuse gliomas, for which we compared two methodologies. The first method provided each model with the free-text tumor descriptions alone, while the second approach additionally provided the models with a Word document of the WHO CNS5. We termed these approaches zero-shot and retrieval-augmented generation (RAG), respectively [&lt;span&gt;2&lt;/span&gt;]. Koga &lt;i&gt;et al&lt;/i&gt; point out that the methodology we describe in our paper as RAG, may be better described as document-grounded generation, or in-context learning.&lt;/p&gt;&lt;p&gt;While we agree with the definition of RAG provided in the letter as it was initially defined [&lt;span&gt;3&lt;/span&gt;], the field has evolved significantly since the approach was first proposed by Lewis &lt;i&gt;et al&lt;/i&gt; in 2020. Three paradigms of RAG are now increasingly recognized: naive RAG, advanced RAG, and modular RAG [&lt;span&gt;4&lt;/span&gt;]. Naive RAG is an approach where the data for indexing are generally obtained offline and converted into a format such as PDF or Word, and uploaded with the query via the context window. Advanced RAG and modular RAG offer specific improvements to address the limitations of naive RAG; however, to achieve this, they utilize more technical approaches.&lt;/p&gt;&lt;p&gt;The intention for our paper was to use naive RAG. We chose this approach as it leverages the easiest possible way for improving an LLM response that would be reproducible by doctors, considering that most doctors would be unable to utilize the application programming interface and programmatically build a RAG pipeline. As discussed by Koga &lt;i&gt;et al&lt;/i&gt;, the key difference between naive RAG and document-grounding lies in how the document is utilized when the model retrieves its response [&lt;span&gt;5&lt;/span&gt;]. Document-grounding submits the document with the user query and is equivalent to inserting the entire document text into the context window [&lt;span&gt;5&lt;/span&gt;]. Whereas with naive RAG, relevant parts of the document are identified by the model and used with the query to dynamically search its database [&lt;span&gt;4&lt;/span&gt;]. Both approaches are examples of in-context learning as they acquire additional knowledge from the prompt without requiring parameter updates [&lt;span&gt;6&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Bereft of transparency from the LLM providers regarding how they process the document once it has been submitted via the graphical user interface, it is difficult to know whether naive RAG or document-grounding was used to formulate a response. To our knowledge, details regarding how appended documents are utilized during a query are not freely available online by ChatGPT, Llama, or Claude. Furthermore, due to the speed of development in the field, technical aspects of how documents are u","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014353","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}

{"title":"Retrieval-augmented generation versus document-grounded generation: a key distinction in large language models","authors":"Shunsuke Koga,&nbsp;Daisuke Ono,&nbsp;Amrom Obstfeld","doi":"10.1002/2056-4538.70014","DOIUrl":"10.1002/2056-4538.70014","url":null,"abstract":"&lt;p&gt;We read with great interest the article by Hewitt &lt;i&gt;et al&lt;/i&gt;., ‘Large language models as a diagnostic support tool in neuropathology’ [&lt;span&gt;1&lt;/span&gt;]. The authors effectively applied large language models (LLMs) to interpreting the WHO classification of central nervous system tumors; however, we wish to address a technical aspect of their study that warrants clarification.&lt;/p&gt;&lt;p&gt;The authors described their approach as retrieval-augmented generation (RAG). Based on the methods described, the study involved attaching a Word document containing the WHO diagnostic criteria to the prompt to guide its responses. We believe that this approach is more accurately described as document-grounded generation rather than true RAG. Document-grounded generation refers to methods where the model generates outputs explicitly based on a preprovided document, which serves as a static reference [&lt;span&gt;2&lt;/span&gt;]. Unlike RAG, which retrieves information dynamically from external sources [&lt;span&gt;3&lt;/span&gt;], document-grounded generation relies entirely on data embedded in the input prompt at the time of execution. In this study, the WHO criteria were provided with the prompt, which allowed the model to use this information without real-time retrieval. This method is a type of in-context learning, relying on curated contextual data embedded in the input [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Our own work provides an example of in-context learning in a different domain, namely image classification. We evaluated GPT-4 Vision (GPT-4V) for classifying histopathological images stained with tau immunohistochemistry, including neuritic plaques, astrocytic plaques, and tufted astrocytes [&lt;span&gt;5&lt;/span&gt;]. Although GPT-4V initially struggled, few-shot learning with annotated examples, which is a specific application of in-context learning, significantly improved its accuracy, matching that of a convolutional neural network model trained on a larger dataset. These findings demonstrate the utility of in-context learning for both text-based and image-based tasks, with the latter presenting unique challenges for LLMs [&lt;span&gt;6&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Although in-context learning is an effective approach, it has limitations worth considering. Since this method uses static data that are preloaded data into the prompt, errors can occur if the information is outdated or inaccurate. In-context learning may also lead to overfitting to the given context, limiting the model's ability to generalize to other scenarios. If the contextual data are overly complex, the model might misinterpret the information or fail to generate accurate outputs [&lt;span&gt;7&lt;/span&gt;]. To ensure reliability, it is important to carefully select the input data, update it regularly, and consider these limitations when designing tasks.&lt;/p&gt;&lt;p&gt;In summary, clarifying the differences between RAG, document-grounded generation, and in-context learning is essential, especially for readers less familiar with these concepts. Nonetheless, we support the au","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014454","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}

{"title":"Immunohistochemistry-based molecular subtypes of urothelial carcinoma derive different survival benefit from platinum chemotherapy","authors":"Csilla Olah,&nbsp;Oleksandr Shmorhun,&nbsp;Gilbert Georg Klamminger,&nbsp;Josefine Rawitzer,&nbsp;Lara Sichward,&nbsp;Boris Hadaschik,&nbsp;Mulham Al-Nader,&nbsp;Ulrich Krafft,&nbsp;Christian Niedworok,&nbsp;Melinda Váradi,&nbsp;Peter Nyirady,&nbsp;Andras Kiss,&nbsp;Eszter Szekely,&nbsp;Henning Reis,&nbsp;Tibor Szarvas","doi":"10.1002/2056-4538.70017","DOIUrl":"10.1002/2056-4538.70017","url":null,"abstract":"<p>Distinct molecular subtypes of muscle-invasive bladder cancer (MIBC) may show different platinum sensitivities. Currently available data were mostly generated at transcriptome level and have limited comparability to each other. We aimed to determine the platinum sensitivity of molecular subtypes by using the protein expression-based Lund Taxonomy. In addition, we assessed the tumor heterogeneity within the primary tumor and between the primary and lymph node (LN) metastatic sites. Thirteen immunohistochemical markers were stained in a tissue microarray with an overall number of 1,508 cores. Statistical evaluation was performed in 199 patients divided into three chemo-naïve MIBC cohorts: (1) pT3/4 and/or LN+ patients who received radical cystectomy without platinum treatment, (2) patients who received adjuvant chemotherapy (AC), and (3) patients who underwent palliative platinum treatment for metastatic disease or postoperative progression. Overall survival (OS) was used as the primary endpoint. Patients with the genomically unstable (GU) subtype had significantly better OS in the AC group compared to the radical cystectomy group (HR: 0.395, 95% CI: 0.205–0.795, <i>p</i> = 0.005). In contrast, no such association was observed for the basal/squamous (Ba/Sq) subtype. Intratumor heterogeneity was present in 19% of cases, with the lowest level in the Ba/Sq and GU tumors (14% each) and the highest level of 43% in small-cell/neuroendocrine-like tumors. There was greater subtype heterogeneity between primary tumors and LN metastases. In conclusion, immunohistochemistry-based Lund Taxonomy subtypes remain stable within the same primary tumor, with the GU subtype deriving the greatest OS benefit from AC. However, high tumor heterogeneity between the primary tumor and metastatic sites can impact the effectiveness of therapies.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014479","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}

{"title":"Loss of MTAP expression is strongly linked to homozygous 9p21 deletion, unfavorable tumor phenotype, and noninflamed microenvironment in urothelial bladder cancer","authors":"Natalia Gorbokon,&nbsp;Niklas Wößner,&nbsp;Viktoria Ahlburg,&nbsp;Henning Plage,&nbsp;Sebastian Hofbauer,&nbsp;Kira Furlano,&nbsp;Sarah Weinberger,&nbsp;Paul Giacomo Bruch,&nbsp;Simon Schallenberg,&nbsp;Florian Roßner,&nbsp;Sefer Elezkurtaj,&nbsp;Maximilian Lennartz,&nbsp;Niclas C Blessin,&nbsp;Andreas H Marx,&nbsp;Henrik Samtleben,&nbsp;Margit Fisch,&nbsp;Michael Rink,&nbsp;Marcin Slojewski,&nbsp;Krystian Kaczmarek,&nbsp;Thorsten Ecke,&nbsp;Tobias Klatte,&nbsp;Stefan Koch,&nbsp;Nico Adamini,&nbsp;Sarah Minner,&nbsp;Ronald Simon,&nbsp;Guido Sauter,&nbsp;Henrik Zecha,&nbsp;David Horst,&nbsp;Thorsten Schlomm,&nbsp;Lukas Bubendorf,&nbsp;Martina Kluth","doi":"10.1002/2056-4538.70012","DOIUrl":"10.1002/2056-4538.70012","url":null,"abstract":"<p>Homozygous 9p21 deletions usually result in a complete loss of S-methyl-5′-thioadenosine phosphorylase (MTAP) expression visualizable by immunohistochemistry (IHC). MTAP deficiency has been proposed as a marker for predicting targeted treatment response. A tissue microarray including 2,710 urothelial bladder carcinomas were analyzed for 9p21 deletion by fluorescence <i>in situ</i> hybridization and MTAP expression by IHC. Data were compared with data on tumor phenotype, patient survival, intratumoral lymphocyte subsets, and PD-L1 expression. The 9p21 deletion rate increased from pTaG2 low (9.2% homozygous, 25.8% heterozygous) to pTaG2 high (32.6%, 20.9%; <i>p</i> &lt; 0.0001) but was slightly lower in pTaG3 (16.7%, 16.7%) tumors. In pT2–4 carcinomas, 23.3% homozygous and 17.9% heterozygous deletions were found, and deletions were tied to advanced pT (<i>p</i> = 0.0014) and poor overall survival (<i>p</i> = 0.0461). Complete MTAP loss was seen in 98.4% of homozygous deleted while only 1.6% of MTAP negative tumors had retained 9p21 copies (<i>p</i> &lt; 0.0001). MTAP loss was linked to advanced stage and poor overall survival in pT2–4 carcinomas (<i>p</i> &lt; 0.05 each). The relationship between 9p21 deletions/MTAP loss and poor patient prognosis was independent of pT and pN (<i>p</i> &lt; 0.05 each). The 9p21 deletions were associated with a noninflamed microenvironment (<i>p</i> &lt; 0.05). Complete MTAP loss is strongly tied to homozygous 9p21 deletion, aggressive disease, and noninflamed microenvironment. Drugs targeting MTAP-deficiency may be useful in urothelial bladder carcinoma. MTAP IHC is a near perfect surrogate for MTAP deficiency in this tumor type.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"11 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819680","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}

{"title":"Large multimodal model-based standardisation of pathology reports with confidence and its prognostic significance","authors":"Ethar Alzaid,&nbsp;Gabriele Pergola,&nbsp;Harriet Evans,&nbsp;David Snead,&nbsp;Fayyaz Minhas","doi":"10.1002/2056-4538.70010","DOIUrl":"10.1002/2056-4538.70010","url":null,"abstract":"<p>Despite the existence of established standards and guidelines for pathology reporting, many pathology reports are still written in unstructured free text. Extracting information from these reports and formatting it according to a standard is crucial for consistent interpretation. Automated information extraction from unstructured pathology reports is a challenging task, as it requires accurately interpreting medical terminologies and context-dependent details. In this work, we present a practical approach for automatically extracting information from unstructured pathology reports or scanned paper reports utilising a large multimodal model. This framework uses context-aware prompting strategies to extract values of individual fields, such as grade, size, etc. from pathology reports. A unique feature of the proposed approach is that it assigns a confidence value indicating the correctness of the model's extraction for each field and generates a structured report in line with national pathology guidelines in human and machine-readable formats. We have analysed the extraction performance in terms of accuracy and kappa scores, and the quality of the confidence scores assigned by the model. We have also evaluated the prognostic value of the extracted fields and feature embeddings of the raw text. Results showed that the model can accurately extract information with an accuracy and kappa score up to 0.99 and 0.98, respectively. Our results indicate that confidence scores are an effective indicator of the correctness of the extracted information achieving an area under the receiver operating characteristic curve up to 0.93 thus enabling automatic flagging of extraction errors. Our analysis further reveals that, as expected, information extracted from pathology reports is highly prognostically relevant. The framework demo is available at: https://labieb.dcs.warwick.ac.uk/. Information extracted from pathology reports of colorectal cancer cases in the cancer genome atlas using the proposed approach and its code are available at: https://github.com/EtharZaid/Labieb.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639939","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}