Pathobiology最新文献_第3页

REV7 Expression Is Associated with Tumor Cell Growth and Cisplatin Resistance in Gallbladder Adenocarcinoma. 在胆囊腺癌中，REV7的表达与肿瘤细胞生长和顺铂耐药有关。

IF 1.7 4区医学

Pathobiology Pub Date : 2026-01-01 Epub Date: 2026-01-09 DOI: 10.1159/000549588

Masahiro Matsushita, Takuya Kato, Yasutaka Sakurai, Masaaki Ichinoe, Taro Kogami, Akihiro Tamaki, Yurika Kesen, Shoko Hayashi, Itaru Sanoyama, Yoshiko Numata, Atsuko Umezawa, Masatoshi Ichihara, Chika Kusano, Yoshiki Murakumo

{"title":"REV7 Expression Is Associated with Tumor Cell Growth and Cisplatin Resistance in Gallbladder Adenocarcinoma.","authors":"Masahiro Matsushita, Takuya Kato, Yasutaka Sakurai, Masaaki Ichinoe, Taro Kogami, Akihiro Tamaki, Yurika Kesen, Shoko Hayashi, Itaru Sanoyama, Yoshiko Numata, Atsuko Umezawa, Masatoshi Ichihara, Chika Kusano, Yoshiki Murakumo","doi":"10.1159/000549588","DOIUrl":"10.1159/000549588","url":null,"abstract":"Introduction: REV7 functions in various biological processes, including the DNA damage response. REV7 expression has been linked to the prognosis and chemoresistance in several human cancers. This study investigated the significance of REV7 in gallbladder adenocarcinoma (GBAC).Methods: REV7 expression was examined immunohistochemically in 77 resected GBAC specimens, and its association with clinicopathological features was analyzed. REV7-depleted GBAC cell lines were established, and the biological effects of REV7 depletion were evaluated.Results: High REV7 expression in GBAC tissues correlated with increased cell proliferation, as assessed by Ki-67 labeling indices (p < 0.001), and was associated with a trend toward shorter overall survival (p = 0.070) and significantly shorter post-progression survival (p = 0.035). REV7-knockout and REV7-knockdown cell lines derived from NOZ and G415 GBAC cells (NOZ-KO and G415-KD, respectively) showed reduced proliferation and increased sensitivity to cisplatin; however, REV7 depletion did not affect cell migration and invasion. Reintroduction of REV7 into NOZ-KO cells restores chemoresistance. Furthermore, RNA sequencing analysis comparing wild-type NOZ and NOZ-KOs revealed that REV7 inactivation downregulates genes involved in the DNA damage response.Conclusion: REV7 may contribute to tumor progression and chemoresistance in GBAC and may serve as a prognostic biomarker and molecular target for GBAC management.","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"187-199"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145945494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Myeloid Neoplasms with Evidence of the Additive/Cumulative Effect of Molecular Genetic Alterations That "Pave the Way" to a Specific Disease Category or Entity: Lessons Learned from Cases Submitted to the 22nd Meeting of the European Association for Haematopathology/Society of Hematopathology Bone Marrow Workshop Organized by the European Bone Marrow Working Group, Dubrovnik 2024. 髓系肿瘤具有分子遗传改变的累加性/累积效应的证据，为特定疾病类别或实体“铺平道路”：从提交给欧洲血液病理学协会/血液病理学学会（EA4HP/SH）第22次会议的病例中吸取的经验教训，该会议由欧洲骨髓工作组（ebwg）组织，杜布罗夫尼克2024。

IF 2 4区医学

Pathobiology Pub Date : 2026-01-01 Epub Date: 2025-10-10 DOI: 10.1159/000548829

Alexandar Tzankov, Anna Green, Roos Leguit, Leonie Saft, Olga K Weinberg, Alexandra Traverse-Glehen

引用次数: 0

Chimeric Antigen Receptor Natural Killer T-Cell Therapy for Tumors: Promise and Progress. CAR-NKT细胞治疗肿瘤：希望与进展

IF 1.7 4区医学

Pathobiology Pub Date : 2026-01-01 Epub Date: 2026-02-28 DOI: 10.1159/000551197

Ruo-Bing Wang, Xuan Wang, Kun-Kun Han, Guo-Dong Chen, Yi-Li Yang, Xin Xu, Tao Zhang

{"title":"Chimeric Antigen Receptor Natural Killer T-Cell Therapy for Tumors: Promise and Progress.","authors":"Ruo-Bing Wang, Xuan Wang, Kun-Kun Han, Guo-Dong Chen, Yi-Li Yang, Xin Xu, Tao Zhang","doi":"10.1159/000551197","DOIUrl":"10.1159/000551197","url":null,"abstract":"Background: Therapy based on chimeric antigen receptor-engineered invariant natural killer T cells (chimeric antigen receptor natural killer T [CAR-NKT] cells) is an innovative cellular immunotherapy strategy that offers advantages over conventional CAR-T cell therapy in the treatment of solid tumors.Summary: This article reviewed the research progress and current application of CAR-NKT cells in solid tumors. Current studies have shown that CAR-NKT cells can efficiently recognize tumor-associated antigens, infiltrate the tumor microenvironment, and exert antitumor effects through direct killing and cytokine secretion. Compared with CAR-T therapy, CAR-NKT therapy exhibits stronger antitumor potency and a reduced incidence of graft-versus-host disease. Furthermore, CAR-NKT cells can enhance antitumor immunity by regulating dendritic cells, NK cells, and CD8+ T cells. Early clinical trials for neuroblastoma and preclinical trials for other solid tumors have shown good safety and preliminary efficacy, and therapies have great potential for clinical translation.Key messages: However, this therapy still faces challenges such as optimizing antigen selection, insufficient in vivo expansion and persistence, tumor heterogeneity, and immune suppression barriers. Future directions include advancing cytokine engineering and combination therapies. Collectively, CAR-NKT cells provide new ideas and new means to break through the difficulties in treating solid tumors and hold the promise of becoming the next generation of cellular immunotherapy.","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"283-295"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

2,3-Pyridinedicarboxylate Is Associated with Shorter Recurrence-Free Survival in Patients with Hypopharyngeal Squamous Cell Carcinoma. 2,3-吡啶二羧酸盐与下咽鳞状细胞癌患者较短的无复发生存期相关。

IF 1.7 4区医学

Pathobiology Pub Date : 2026-01-01 Epub Date: 2025-08-26 DOI: 10.1159/000548128

Hiroki Takase, Takao Fujisawa, Ryuichi Hayashi, Hideki Makinoshima, Yutaka Suzuki, Tomoyoshi Soga, Satoshi Fujii

{"title":"2,3-Pyridinedicarboxylate Is Associated with Shorter Recurrence-Free Survival in Patients with Hypopharyngeal Squamous Cell Carcinoma.","authors":"Hiroki Takase, Takao Fujisawa, Ryuichi Hayashi, Hideki Makinoshima, Yutaka Suzuki, Tomoyoshi Soga, Satoshi Fujii","doi":"10.1159/000548128","DOIUrl":"10.1159/000548128","url":null,"abstract":"Introduction: Metabolites are associated with the biology of cancer; however, no metabolites related to prognosis have been identified in head and neck cancer. This study aimed to identify metabolites associated with prognosis in patients with hypopharyngeal squamous cell carcinoma (HPSCC).Methods: Fifty-two patients who underwent surgery for HPSCC were included and randomly divided into test and validation cohorts of 26 patients each for further metabolome analysis using capillary electrophoresis/mass spectrometry on tumor and non-tumor tissues of the hypopharynx. Twenty-two patients who received adjuvant therapy after surgery were included. The receiver operating characteristic (ROC) and univariate and multivariate analyses were used to explore the relationship between recurrence-free survival (RFS), clinicopathological factors, and differentiated metabolites.Results: ROC analysis revealed six metabolites significantly associated with RFS in both cohorts, and multivariate analysis indicated that 2,3-pyridinedicarboxylate was a significantly independent poorer prognostic factor in the cohorts including patients with HPSCC without any adjuvant therapies (p = 0.017).Conclusion: 2,3-Pyridinedicarboxylate, involved in NAD+ metabolism and genomic stability, suggests the possibility of developing molecular-targeted drugs for the production of metabolites related to prognosis. This study identifies novel prognostic metabolites and their associated metabolic pathways in HPSCC, highlighting potential therapeutic targets for treatment. .","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"72-86"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Erratum. 勘误表。

IF 2 4区医学

Pathobiology Pub Date : 2026-01-01 Epub Date: 2026-04-08 DOI: 10.1159/000550993

引用次数: 0

Assessing Tumour Budding in Lung Squamous Cell Carcinoma: A Comparative Analysis of Digital Whole-Slide Imaging and Light Microscopy. 评估肺鳞状细胞癌的肿瘤萌芽：数字全切片成像与光学显微镜的比较分析。

IF 1.7 4区医学

Pathobiology Pub Date : 2026-01-01 Epub Date: 2025-11-24 DOI: 10.1159/000549728

Mark Keyter, Stefano Lucà, Marie Maillard, Solange Peters, Thorsten Krueger, Sabina Berezowska

{"title":"Assessing Tumour Budding in Lung Squamous Cell Carcinoma: A Comparative Analysis of Digital Whole-Slide Imaging and Light Microscopy.","authors":"Mark Keyter, Stefano Lucà, Marie Maillard, Solange Peters, Thorsten Krueger, Sabina Berezowska","doi":"10.1159/000549728","DOIUrl":"10.1159/000549728","url":null,"abstract":"Introduction: Tumour budding (TB) is an emerging prognostic marker in solid cancers and has recently been endorsed by the IASLC as a component of grading in lung squamous cell carcinoma (LUSC). With the growing adoption of digital pathology, the reproducibility of TB assessment on whole-slide images (WSIs) warrants evaluation.Methods: We assessed the utility of WSI for TB evaluation in a retrospective cohort of 204 resected LUSC cases. Peritumoral budding (PTB) and intratumoural budding (ITB) were independently scored by two pathologists, applying the International Tumour Budding Consensus Conference (ITBCC) criteria established for colorectal cancer and endorsed by the IASLC for use in LUSC. A total of 816 TB hotspot regions were analysed.Results: Substantial intraobserver reliability was observed, with strong correlations between absolute bud counts in WSI and conventional light microscopy (CLM; R = 0.845, p < 0.001; R = 0.880, p < 0.001). Interobserver agreement was moderate for both PTB and ITB across platforms (Cohen's κ: CLM 0.582 [PTB], 0.570 [ITB]; WSI 0.593 [PTB], 0.423 [ITB]). Discordance mainly occurred in lower TB categories due to differences in hotspot selection and morphological mimics. When applying the recently proposed IASLC two-tier cutoff (0-9 buds vs. ≥10 buds), interobserver agreement for PTB improved modestly (κ = 0.49 for CLM; κ = 0.53 for WSI), with overall agreement exceeding 93%.Conclusion: These findings support the feasibility and reproducibility of TB assessment using WSI and highlight its potential for standardizing LUSC TB evaluation in digital pathology workflows. WSI also demonstrated practical advantages, including easier field selection and annotation. .","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"135-146"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12788830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Malignant Progression of Subependymal Giant Cell Astrocytoma-Imitating Fibrous Meningioma in a Child Carrying a Germline CHEK2 Mutation. 携带种系CHEK2突变的儿童的sega -模仿纤维脑膜瘤的恶性进展

IF 1.7 4区医学

Pathobiology Pub Date : 2026-01-01 Epub Date: 2026-01-27 DOI: 10.1159/000550591

Bartosz Szmyd, Marcin Braun, Agata Pastorczak, Dariusz Jan Jaskólski, Joanna Madzio, Karolina Miarka-Walczyk, Zuzanna Urbańska, Wiesława Grajkowska, Joanna Trubicka, Dariusz Adamek, Dobromiła Barańska, Wojciech Młynarski, Joanna Trelińska

{"title":"Malignant Progression of Subependymal Giant Cell Astrocytoma-Imitating Fibrous Meningioma in a Child Carrying a Germline <italic>CHEK2</italic> Mutation.","authors":"Bartosz Szmyd, Marcin Braun, Agata Pastorczak, Dariusz Jan Jaskólski, Joanna Madzio, Karolina Miarka-Walczyk, Zuzanna Urbańska, Wiesława Grajkowska, Joanna Trubicka, Dariusz Adamek, Dobromiła Barańska, Wojciech Młynarski, Joanna Trelińska","doi":"10.1159/000550591","DOIUrl":"10.1159/000550591","url":null,"abstract":"Introduction: The subependymal giant cell astrocytoma (SEGA) predominantly occurs in patients with tuberous sclerosis. Here, we present an unusual aggressive transformation of SEGA-imitating fibrous meningioma in a child carrying a germline CHEK2 mutation.Methods: This case study was conducted at a tertiary pediatric oncology center in accordance with current diagnostic and therapeutic standards. Tumor classification followed WHO CNS5 criteria and was complemented by genome-wide DNA methylation profiling. Comprehensive molecular workup included germline and somatic whole exome sequencing, copy number analysis, and RNA sequencing.Results: An 8.5-year-old girl presented with an intraventricular tumor initially diagnosed as SEGA based on imaging and partial resection histology. Treatment with an mTOR inhibitor led to 4 years of stability before rapid progression and death due to postoperative brain edema. Re-examination of both specimens revealed transformation into an aggressive anaplastic meningioma, while the initial lesion was reclassified as fibrous meningioma. Whole exome and microarray analyses excluded germline TSC1/TSC2 defects but identified a pathogenic germline CHEK2 variant (c.1466del, p.Asn489ThrfsTer23). Somatic alterations involving NF1 and TP53 were found in the primary tumor.Conclusions: Constitutional CHEK2 mutations combined with somatic NF1 defect may have promoted the malignant progression of SEGA-imitating fibrous meningioma and its favorable initial response to mTOR inhibitors.","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"246-254"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146065872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FAT1 Is Differentially Expressed in Cancers Affecting the Serosal Cavities. FAT1在影响浆膜腔的癌症中有差异表达。

IF 1.7 4区医学

Pathobiology Pub Date : 2026-01-01 Epub Date: 2026-03-27 DOI: 10.1159/000551734

Ben Davidson, Arild Holth

{"title":"FAT1 Is Differentially Expressed in Cancers Affecting the Serosal Cavities.","authors":"Ben Davidson, Arild Holth","doi":"10.1159/000551734","DOIUrl":"10.1159/000551734","url":null,"abstract":"Introduction: FAT1 is mutated in many types of cancer. The objective of this study was to analyze the diagnostic role of FAT1 protein in cancers affecting the serosal cavities.Methods: FAT1 protein expression by immunohistochemistry was analyzed in 256 effusions (139 peritoneal, 116 pleural, 1 pericardial), consisting of 96 tubo-ovarian carcinomas, 56 breast carcinomas, 44 mesotheliomas, 28 uterine corpus and cervical carcinomas, 15 lung carcinomas, 13 gastrointestinal carcinomas, and 4 cancers of other origin.Results: FAT1 expression was most common in gastrointestinal carcinomas (12/13; 92%), followed by lung (9/15; 60%), breast (31/56; 55%), and uterine cervical (4/8; 50%) carcinomas, with infrequent expression in other tumors, including tubo-ovarian carcinomas (5/96; 5%). Mesotheliomas were uniformly negative. Staining of a limited series of surgical specimens showed comparable results for patient-matched breast carcinomas (29/41; 71%), whereas tubo-ovarian carcinomas were more frequently positive (16/57; 28%), though often focally, compared to effusions. Eight epithelioid mesotheliomas were negative (0/8; 0%). Survival analysis for 42 breast carcinoma patients with effusion for whom clinical data were available showed no association with overall (p = 0.398) or disease-free (p = 0.255) survival.Conclusion: FAT1 is commonly expressed in carcinomas of gastrointestinal, lung, or breast origin but is rarely expressed in tubo-ovarian carcinoma effusions and is absent in mesothelioma. Whether this difference is of use in the diagnostic setting remains to be established.","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"255-262"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147531721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unravelling the Tumourigenesis Mechanisms of Oncocytic Cell Tumours: Discoveries from a Comparative Omics Study. 揭示嗜瘤细胞肿瘤的发生机制：来自比较组学研究的发现。

IF 2 4区医学

Pathobiology Pub Date : 2026-01-01 Epub Date: 2025-10-28 DOI: 10.1159/000548985

Sule Canberk, Marta Ferreira, Arnaud Da Cruz Paula, Luísa Pereira, Carla Oliveira, Hugo Osório, Paula Soares, Valdemar Máximo

{"title":"Unravelling the Tumourigenesis Mechanisms of Oncocytic Cell Tumours: Discoveries from a Comparative Omics Study.","authors":"Sule Canberk, Marta Ferreira, Arnaud Da Cruz Paula, Luísa Pereira, Carla Oliveira, Hugo Osório, Paula Soares, Valdemar Máximo","doi":"10.1159/000548985","DOIUrl":"10.1159/000548985","url":null,"abstract":"Introduction: Oncocytic cell tumours (OCTs), previously referred to as Hürthle cell tumours of the thyroid, are a subset of thyroid and endocrine neoplasms that pose diagnostic and therapeutic challenges owing to their unpredictable clinical behaviour. The transcriptomic and proteomic landscapes of OCTs remain poorly characterized compared with those of mitochondrion-rich neoplasms (MRNs: thyroid tumours with ≥75% oncocytic cells that share similar morphology but harbour nuclear driver mutations consistent with their respective histotypes rather than mitochondrial alterations).Methods: We performed RNA and protein sequencing on 12 OCT samples and 6 MRNs. This study was prompted by the understanding that oncocytic morphology alone does not necessarily predict tumour behaviour.Results: RNA sequencing analysis identified 47 downregulated and 38 upregulated differentially expressed genes (DEGs) in OCTs relative to MRNs, with significant enrichment in pathways related to heme metabolism. Protein sequencing further revealed 20 under-expressed and 64 over-expressed differentially expressed proteins (DEPs) in OCTs. Notably, all oncocytic carcinomas formed a distinct cluster separate from the MRNs, indicating a unique proteomic profile.Conclusion: Most of the DEPs were involved in three key cellular pathways: epigenetic regulation, the tumour microenvironment, and protein biogenesis, suggesting that these processes may underlie the distinctive morphology and behaviour of OCTs. These findings highlight the need for continued research into these molecular mechanisms to improve the diagnostic accuracy and develop targeted therapies for patients with OCTs.","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"109-122"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145392147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advances in Renal Cell Carcinoma Diagnosis: A Review on Biomarkers. 肾细胞癌诊断的生物标志物研究进展

IF 1.7 4区医学

Pathobiology Pub Date : 2026-01-01 Epub Date: 2026-01-27 DOI: 10.1159/000550723

Agnese Orsatti, Fernanda Fernandes-Pontes, João Ricardo E Silva, Nuno Tiago Tavares, Carmen Jerónimo, Rui Henrique, Ângelo Rodrigues, Costantino Ricci, João Lobo

{"title":"Advances in Renal Cell Carcinoma Diagnosis: A Review on Biomarkers.","authors":"Agnese Orsatti, Fernanda Fernandes-Pontes, João Ricardo E Silva, Nuno Tiago Tavares, Carmen Jerónimo, Rui Henrique, Ângelo Rodrigues, Costantino Ricci, João Lobo","doi":"10.1159/000550723","DOIUrl":"10.1159/000550723","url":null,"abstract":"Background: Renal cell carcinoma (RCC) is a heterogeneous disease, with the last World Health Organization (WHO) classification introducing several novel entities, among which the molecularly defined RCCs. This growing complexity highlights the need for integration of morphology, immunohistochemistry (IHC) and molecular techniques, ensuring accurate classification and reducing the \"RCC not otherwise specified (NOS) category.\"Summary: Molecular assays such as next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH) are increasingly necessary for diagnosing molecularly defined RCCs. IHC remains fundamental for diagnosing both \"old\" and newly defined RCCs, representing a surrogate for molecular alterations such as fumarate-hydratase and succinate-dehydrogenase deficiency, anaplastic lymphoma kinase rearrangements, SMARCB1 loss, and TFE3 rearrangements. However, entities like ELOC-mutated RCC require molecular testing for diagnosis. Liquid biopsy offers a further diagnostic tool. Circulating microRNAs can support diagnosis, classification, and monitoring. Furthermore, circulating tumor DNA (ctDNA) methylation analyses and circulating tumor cells (CTCs) offer promising and minimally invasive tools for stratification, though their clinical use is still evolving.Key messages: A precise diagnosis integrating histopathology, IHC, and molecular testing is critical for guiding management, identifying hereditary syndromes, and implementing personalized tumor biology-based therapies. With evolving molecular diagnostic and circulating biomarkers, careful clinical integration is needed to optimize outcomes and treatment.","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"263-282"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146065897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0