Virchows Archiv最新文献

{"title":"Identification of a novel RAB6A::TOP2A fusion in acute non-promyelocytic leukemia harboring t(11;17)(q13;q21) translocation.","authors":"Zhan Su, Yahui Du, Chenglu Yuan, Xianzhi Zhao, Xiaoshan Zhang, Hongqing Cui, Ting Yue, Hongguo Zhao, Wei Wang","doi":"10.1007/s00428-024-03853-1","DOIUrl":"10.1007/s00428-024-03853-1","url":null,"abstract":"<p><p>Fusion genes generally serve as driver mutations in leukemia. The rearrangement of the RARA gene located on chromosome 17q21 is a molecular pathological feature of acute promyelocytic leukemia (APL). A series of RARA-involved fusion genes have been identified in variant APL, including one carrying the t(11;17)(q13;q21) translocation, resulting in the NUMA1::RARA fusion gene. Here, we present an interesting case where blasts carry the t(11;17)(q13;q21), but the cell morphology does not exhibit signs of promyelocytic differentiation. Transcriptome sequencing identified a novel fusion gene, RAB6A::TOP2A, with a frameshift mutation in the reading frame. The patient did not respond to all-trans retinoic acid (ATRA) treatment.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"1355-1358"},"PeriodicalIF":3.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic role of claudin-18.2 in intrahepatic cholangiocarcinoma.","authors":"Yu-Hsuan Kuo, Khaa Hoo Ong, Ding-Ping Sun, Yu-Feng Tian, Chia-Ling Chou, Ti-Chun Chan, Chung-Hsi Hsing, Wan-Shan Li, Chien-Feng Li, Yow-Ling Shiue","doi":"10.1007/s00428-025-04081-x","DOIUrl":"10.1007/s00428-025-04081-x","url":null,"abstract":"<p><p>Claudins are key components of tight junctions, essential for maintaining cellular adhesion, regulating intercellular molecule transport, and preserving cell polarity. Altered claudin expression can lead to tight junction dysfunction, potentially disrupting signaling pathways and contributing to the development of epithelial cancers. This study aims to explore the understudied role of CLDN18.2 in intrahepatic cholangiocarcinoma and its relationship with clinical outcomes. We analyzed tissue samples from 182 patients who underwent curative surgery for intrahepatic cholangiocarcinoma. Our research examined the relationship between CLDN18.2 expression and various clinical factors, including patient characteristics, pathological findings, and survival metrics such as overall survival (OS), disease-free survival (DFS), metastasis-free survival (MeFS), and local recurrence-free survival (LRFS). Overexpression of CLDN18.2 showed significant associations with R1 resection (p = 0.032) and advanced T stage (p = 0.043). Univariate analysis revealed that high CLDN18.2 expression was correlated with poorer OS (p = 0.0002), DFS (p < 0.0001), LRFS (p < 0.0001), and MeFS (p < 0.0001). Multivariate analysis further confirmed that high CLDN18.2 expression was independently associated with worse OS (p = 0.015), DFS (p < 0.001), LRFS (p < 0.001), and MeFS (p < 0.001). Overexpression of CLDN18.2 was associated with unfavorable clinical prognosis and adverse pathological features in intrahepatic cholangiocarcinoma. These findings suggest that CLDN18.2 could serve as a potential prognostic biomarker for intrahepatic cholangiocarcinoma.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"1199-1210"},"PeriodicalIF":3.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP- 1R status using validated monoclonal antibody in 689 cases of neuroendocrine neoplasm and its correlation with somatostatin receptor scintigraphy, insulin production, and histological grades.","authors":"Hirofumi Watanabe, Fumiyoshi Fujishima, Yuto Yamazaki, Masayuki Imamura, Susumu Hijioka, Kazuo Hara, Takamichi Kuwahara, Yasushi Yatabe, Kazuhiro Sakamoto, Hisashi Shiga, Tomohiro Kawaguchi, Hiroyoshi Suzuki, Yumi Kanbayashi, Akira Ohkoshi, Muneaki Shimada, Hiromichi Niikawa, Mami Sato, Atsushi Fujio, Toshihiko Masui, Yosuke Kasai, Hideki Ota, Hiroshi Ozawa, Hidenori Endo, Michiaki Unno, Hironobu Sasano, Takashi Suzuki","doi":"10.1007/s00428-025-04098-2","DOIUrl":"10.1007/s00428-025-04098-2","url":null,"abstract":"<p><p>Radiolabeled glucagon-like peptide 1 (GLP- 1) analog scintigraphy is a new, high-sensitivity imaging method for detecting small insulinomas. Somatostatin receptor scintigraphy (SRS) is an established method for detecting gastroenteropancreatic neuroendocrine tumors. However, small benign insulinomas are difficult to detect using SRS. Furthermore, GLP- 1 receptor (GLP- 1R) expression and SRS results may be inversely correlated. We identified 689 neuroendocrine neoplasms, including pancreatic neuroendocrine tumors (PanNETs) and neuroendocrine neoplasms originating from non-pancreatic sites, and performed GLP- 1R immunostaining. Among the non-insulinoma PanNETs, immunohistochemical insulin or proinsulin positive cases were categorized as Ins_pos, and both negative cases as Ins_neg. High prevalence of GLP- 1R expression was detected in PanNETs and duodenal NETs (34% and 53%, respectively). Some pulmonary NETs were GLP- 1R positive (9%). In contrast, neither GI-NEC excluding one case nor pulmonary NEC exhibited GLP- 1R expression. The percentage of GLP- 1R positive cases for Ins_pos, Ins_neg, and insulinoma was 31%, 0%, and 84%, respectively. Among PanNETs, GLP- 1R positive cases showed higher expression of insulin and proinsulin than negative cases. SRS-positive patients showed lower expression levels of insulin, proinsulin, and GLP- 1R than SRS-negative patients. The expression in PanNETs and duodenal NETs may be derived from the expression in their normal counterparts. Insulinoma and Ins_pos cases showed GLP- 1R expression. Furthermore, as GLP- 1R-positive patients showed significantly higher expression of insulin and proinsulin than GLP- 1R negative patients, GLP- 1R may also be associated with neoplastic insulin production and GLP- 1 analog scintigraphy may detect subclinical insulinomas. In addition, SRS-negative cases showed significantly higher GLP- 1R expression than SRS-positive cases. These results suggest the application potential of GLP- 1 analog scintigraphy in combination with SRS as a detection tool.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"1317-1326"},"PeriodicalIF":3.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S100 and CD34 positive spindle cell tumors of the uterine cervix with EGFR mutation: a hitherto unrecognized neoplasm phenotypically and epigenetically overlapping with \"NTRK-rearranged spindle cell neoplasms\" of the uterus.","authors":"Michael Michal, Josef Kuruc, Veronika Hájková, Květoslava Michalová, Natálie Klubíčková","doi":"10.1007/s00428-024-03936-z","DOIUrl":"10.1007/s00428-024-03936-z","url":null,"abstract":"<p><p>NTRK-rearranged spindle cell neoplasm represents an emerging entity included in the latest 5th edition of WHO classification of both soft tissue and female genital tumors. By immunohistochemistry, they are commonly positive for CD34, S100 protein, and CD30 and typically harbor fusions of kinase genes such as NTRK1/2/3, RET, and BRAF. In the gynecological tract, they typically affect the uterine cervix or uterine body. Most of the reported cases had fibrosarcoma-like morphology, occasionally showing perivascular and stromal hyalinization with only a few cases showing a less cellular spindle cell proliferation. Except for one case with RET fusion, all other gynecological cases harbored exclusively NTRK1/2/3 fusions. Besides kinase gene fusions, the analogous tumors in soft tissues may also harbor activating EGFR or BRAF point mutations, but no such case has been described in the uterus. Herein we are reporting two cases from the uterine cervix showing morphology and molecular features previously unreported at this anatomic site. The patients were 46 and 34 years old and clinically presented with unremarkable cervical polyps each measuring 8 mm in diameter. Histologically, both cases had a rounded polypoid outline and were composed of hypocellular proliferation of bland spindle cells lacking mitotic activity and growing in a fibrotic stroma which was punctuated by prominent small vessels with thick hyalinized walls. Immunohistochemically, both showed a diffuse expression of CD34, CD30, and S100 protein, whereas SOX10 was negative. Both cases harbored exon 20 EGFR mutation and did not reveal any fusions or significant copy number changes. The patient in case 1 was treated by hysterectomy with salpingectomy with no other residual tumor detected, and she was alive and well 27 months after the diagnosis. The patient in case 2 had no other known tumors at the time of diagnosis, but no follow-up is available. We believe the reported cases represent a hitherto unrecognized variant of \"NTRK-rearranged spindle cell neoplasms\" of the uterine cervix with novel EGFR mutations.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"1211-1219"},"PeriodicalIF":3.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sensitive and reliable detection of KIT p.D816V mutation in decalcified archival bone marrow trephines.","authors":"Miriam Odensass, Stephan Bartels, Jerome Schlue, Guntram Büsche, Hans H Kreipe, Ulrich Lehmann","doi":"10.1007/s00428-024-03973-8","DOIUrl":"10.1007/s00428-024-03973-8","url":null,"abstract":"<p><p>The majority of mastocytosis cases are characterized by an activating mutation in the KIT gene in codon 816. The detection of this alteration is of importance for proper diagnostic workup. Therefore, reliable and sensitive methods for the detection of KIT Codon 816 hotspot mutations in various types of patient samples are required. Since mutated cancer genes are often overexpressed, we evaluated the feasibility and sensitivity of KIT p.D816V detection by analysing mRNA/cDNA instead of genomic DNA. From 80 bone marrow trephines harboring a KIT p.D816 mutation, seven were only mutated by mRNA/cDNA pyrosequencing and 11 only by digital PCR analysis of genomic DNA. These results clearly demonstrate that detection of clinically relevant mutations in mRNA extracted from routinely processed decalcified archival bone marrow trephines is not only possible in a reliable fashion but under many circumstances advantageous. This enables the direct correlation of genomic data with high-quality morphological evaluation.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"1349-1353"},"PeriodicalIF":3.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel tumor budding and cell nest size-based grading system outperforms conventional methods in vulvar squamous cell carcinoma.","authors":"Xiangyu Chen, Shuang Song, Haiyan Shi, Bingjian Lu","doi":"10.1007/s00428-025-04123-4","DOIUrl":"10.1007/s00428-025-04123-4","url":null,"abstract":"<p><p>The tumor budding and tumor cell nest size-based (TBNS) grading scheme is an emerging prognostic indicator for squamous cell carcinoma (SCC) across various organs; however, its significance in vulvar SCC (VSCC) remains poorly investigated. In this study, we applied the TBNS grading system to an institutional cohort of 62 consecutive surgically resected VSCC cases (39 HPV-independent and 23 HPV-associated), excluding patients with neoadjuvant chemotherapy or FIGO stage IA disease. High tumor budding activity, small cell nest size, and high TBNS grade were significantly associated with reduced overall survival (OS) and disease-free survival (DFS) in VSCC, as well as with adverse clinicopathologic features such as lymphovascular space invasion, perineural involvement, lymph node metastasis, and advanced FIGO stage (p < 0.05). Multivariate analysis revealed that TBNS grade 3 was independently associated with reduced DFS (p < 0.05). In contrast, among the two conventional grading systems, only the Gynecology Oncology Group grading system showed a significant association with OS in univariate analysis (p < 0.05), but not in multivariate analysis (p > 0.05). We conclude that the TBNS grading system is a promising prognostic indicator for VSCC, outperforming conventional grading systems. Further validation in larger cohorts is needed to expand the clinical applicability of this grading system in VSCC.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"1257-1267"},"PeriodicalIF":3.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunohistochemical analysis of 147 cases of low-grade endometrial stromal sarcoma: refining the immunohistochemical profile of LG-ESS on a large, molecularly confirmed series.","authors":"Miroslava Flídrová, Pavel Dundr, Romana Vránková, Kristýna Němejcová, David Cibula, Renata Poncová, Květoslava Michalová, Jiří Bouda, Jan Laco, Munachiso Ndukwe, Janusz Ryś, Mariusz Książek, Alberto Berjon, Ignacio Zapardiel, Ivan Franin, Antonela Njavro, Jitka Hausnerová, Petra Bretová, Vladimír Židlík, Jaroslav Klát, Zoard Tibor Krasznai, Robert Poka, Nataliya Volodko, Iryna Yezhova, Radovan Pilka, Radim Marek, Georgina Kolnikova, Milan Krkoška, Michael Halaška, Jana Drozenová, Dagmar Dolinská, Vladimír Kalist, Marcin Bobiński, Marta Ostrowska-Leśko, Magdalena Bizoń, Włodzimierz Sawicki, Maciej Stukan, Karolina Grabowska, Marcin Jędryka, Tymoteusz Poprawski, Simona Stolnicu, Mihai Emil Căpîlna, Zuzana Špůrková, Michal Zikán, Francesca Ciccarone, Giovanni Scambia, Archil Sharashenidze, Miranda Gudadze, Tetiana Piatnytska, Ihor Varchak, Michaela Kendall Bártů","doi":"10.1007/s00428-025-04026-4","DOIUrl":"10.1007/s00428-025-04026-4","url":null,"abstract":"<p><p>Low-grade endometrial stromal sarcoma (LG-ESS) can present diagnostic challenges, due to its overlapping morphological features with other uterine mesenchymal tumors. Misdiagnosis rates remain significant, and immunohistochemical data for LG-ESS are limited to small series and inconsistent antibody panels. This study aimed to refine the IHC profile of LG-ESS by analyzing a large, molecularly confirmed series of 147 cases using a panel of 24 antibodies, including newer markers like transgelin and smoothelin. CD10 and IFITM1, key endometrial stromal markers, were expressed in 86% (92% of those extensively) and 69% (60% of those extensively) of cases, with fusion-positive tumors showing significantly higher expression. Smooth muscle markers (α-SMA, desmin, h-caldesmon, calponin, transgelin) were variably expressed, predominantly in focal or low-intensity patterns, with α-SMA reaching the highest frequency of expression (44%). However, the intensity of smooth muscle marker expression was usually very low. Smoothelin was rarely expressed. Hormone receptors were frequently positive, with PR showing a higher frequency (92% vs. 83%) and intensity than ER. Markers like S-100, HMB45, and CD117 were largely negative; all tumors were p53 wild-type, with preserved SMARCB1/SMARCA4 expression and ALK and ROS1 negativity. This work represents the largest molecularly validated IHC study on LG-ESS, providing a robust diagnostic profile for routine pathology. By addressing key diagnostic limitations and examining newer markers, our study supports a more standardized approach to diagnosing LG-ESS and underscores the value of immunohistochemical panels, particularly in fusion-negative tumors where diagnosis relies on morphological and immunohistochemical interpretation. These findings contribute critical data for improving diagnostic accuracy.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"1289-1304"},"PeriodicalIF":3.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary cutaneous rhabdomyosarcoma with EWSR1/FUS::TFCP2 fusion: four new cases with distinctive morphology, immunophenotypic, and genetic profile.","authors":"Isidro Machado, Eva Wardelmann, Ming Zhao, Jing Song, Yanli Wang, Stephan Alexander Braun, Lluís Catasús, Malena Ferré, Irina Leoveanu, Jula Westhoff, Thomas Rüdiger, Sílvia Bagué","doi":"10.1007/s00428-024-04007-z","DOIUrl":"10.1007/s00428-024-04007-z","url":null,"abstract":"<p><p>EWSR1/FUS::TFCP2-rearranged rhabdomyosarcoma (RMS) is a rare tumor with an aggressive clinical course, a predilection for craniofacial bones, spindled and/or epithelioid histomorphology, and positive immunohistochemistry (IHC) for epithelial and myogenic markers, along with variable ALK expression. Herein, we present four additional cases of primary cutaneous TFCP2-rearranged RMS. Notably, one tumor (case 1) displayed a varied pathological spectrum, initially presenting as a low-grade spindle cell neoplasm, but progressed into a high-grade spindle/epithelioid tumor. Another case (case 2) exhibited a predominant high-grade epithelioid/rhabdoid morphology. The third case (case 3) demonstrated a biphasic appearance of spindle and epithelioid cell proliferation, presenting with a low-grade morphology, and the last case (case 4) showed a predominant epithelioid morphology. All cases showed myogenic differentiation associated with keratins and ALK immunoreactivity. Interestingly, the two cases with high-grade and epithelioid morphology demonstrated CD30 immunoexpression. RNAseq or FISH revealed EWSR1 or FUS::TFCP2 gene fusion, and two cases with aggressive evolution showed ALK cluster-amplification as well, a finding that has not been previously reported. Two cases displayed aggressive behavior, with case 1 experiencing local recurrences and undergoing transformation into a high-grade epithelioid tumor, whereas case 2 initially presented as an epithelioid high-grade neoplasm, subsequently developing lymph node metastases and shortly thereafter distant metastases. In contrast, patients 3 and 4 are alive with no evidence of disease. The distinctive morphology and immunoprofile of this neoplasm may pose challenges in the differential diagnosis with cutaneous neoplasms showing keratins, ALK, and CD30 immunoreactivity. Nonetheless, ALK and CD30 overexpression may offer avenues for targeted therapy.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"1187-1198"},"PeriodicalIF":3.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interstitial lipoid pneumonia-A complication of intravenous administration of lipid emulsions in critically ill patients.","authors":"E M V de Cuba, W Vreuls, C G Tan, D B Flieder, E Thunnissen","doi":"10.1007/s00428-024-04000-6","DOIUrl":"10.1007/s00428-024-04000-6","url":null,"abstract":"<p><p>Lipoid pneumonia is a rare entity most often associated with inhalation of foreign material (i.e. \"fire-eater's lung\"), silicone injection, and severe trauma. We present the case of a 61-year old man who developed acute respiratory distress syndrome following endoscopic retrograde cholangiopancreatography (ERCP) for cholelithiasis. Intensive care supportive therapy included mechanical ventilation, dialysis, and total parenteral nutrition. Unresolved pneumothorax necessitated lobectomy. Histology of the lobectomy specimen demonstrated massive intra-alveolar haemorrhage and numerous alveolar septal macrophages with clear cytoplasmic vacuoles. These findings were diagnostic of interstitial lipoid pneumonia due to intravenous administration of lipid emulsions. The differential diagnosis is also discussed. Although rare, interstitial lipoid pneumonia should be considered in critically ill patients presenting with an interstitial pattern of lung disease after intravenous administration of lipid emulsions.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"1339-1343"},"PeriodicalIF":3.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGFR3 amplification is predictive of poor prognosis in esophageal squamous cell carcinoma patients.","authors":"Xiang Wang, Jie Huang, Chen Xu, Lili Zhang, Jieakesu Su, Jia Liu, Licheng Shen, Lijuan Luan, Yingyong Hou","doi":"10.1007/s00428-024-03884-8","DOIUrl":"10.1007/s00428-024-03884-8","url":null,"abstract":"<p><p>Identification and verification of clinically actionable molecular variations to refine currently adopted risk-stratified treatment strategy for esophageal squamous cell carcinoma (ESCC) is urgently needed. Here, we evaluated FGFR3 amplification status by fluorescence in situ hybridization (FISH) performed on tissue microarrays and its prognostic value in 526 ESCC patients. FGFR3 amplification was found in 3.0% (16/526) of ESCC patients enrolled in this study cohort. Intratumor heterogeneity and metastatic heterogeneity of FGFR3 amplification were found in 10% (2/20) and 40% (2/5) FGFR3 amplified ESCC cases, respectively. No statistically significant associations were found between FGFR3 amplification status and common clinicopathological features. Survival analyses demonstrated that FGFR3 amplification was associated with a worse disease-free survival (DFS) and overall survival (OS) (DFS, P = 0.008; OS, P = 0.027). Univariate and multivariate analyses revealed that invasive depth was significantly associated with DFS (P = 0.001, HR: 1.498, 95% CI: 1.172-1.914) and OS (P = 0.002, HR: 1.482, 95% CI: 1.159-1.894), and FGFR3 amplification was significantly associated with DFS (P = 0.020, HR: 2.065, 95% CI: 1.120-3.808) and tend to associate with OS (P = 0.070, HR: 1.756, 95% CI: 0.954-3.233). Furthermore, when patients were stratified into stage I-II group and stage III-IV group, the adverse effect of FGFR3 amplification on prognosis was presented in stage III-IV patients (DFS, P = 0.0047; OS, P = 0.029) rather than stage I-II patients (DFS, P = 0.46; OS, P = 0.53), indicating that the prognostic value of FGFR3 amplification may relying on clinical stage. Our findings might provide a better understanding of the FGFR3 amplification status in ESCC patients and add further insights into its potential prognostic value.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"1153-1164"},"PeriodicalIF":3.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}