https://hdl.handle.net/20.500.14178/904 Thu, 30 Jul 2026 10:56:57 GMT 2026-07-30T10:56:57Z https://hdl.handle.net/20.500.14178/3887 Clinicopathological, Molecular, and DNA Methylation Analysis of Ossifying Fibromyxoid Tumors Delineates the ZC3H7B::BCOR Subset as a Distinct Entity Klubíčková, Natálie; Dermawan, Josephine K; Ameline, Baptiste; Martínek, Petr; Vaněček, Tomáš; Hájková, Veronika; Ptáková, Nikola; Grossmann, Petr; Šteiner, Petr; Kormunda, Stanislav; Perret, Raul E; Le Loarer, François; Dehner, Carina; Torres-Mora, Jorge; Gross, John M; Chrisinger, John S A; Charville, Gregory; Kosemehmetoglu, Kemal; Wangsiricharoen, Sintawat; Meis, Jeanne; Špůrková, Zuzana; Zámečník, Michal; Zambo, Iva Staniczková; Klinger, Tomáš; Švajdler, Marián; Kinkor, Zdeněk; Michalová, Květoslava; Baumhoer, Daniel; Michal, Michal; Antonescu, Cristina R; Michal, Michael Ossifying fibromyxoid tumor (OFMT) is a rare mesenchymal neoplasm of uncertain lineage of differentiation driven by a broad spectrum of gene fusions. It manifests primarily in soft tissues of the extremities. In this study, we performed a comprehensive clinicopathological, molecular-genetic, and epigenetic analysis of 70 cases of OFMT, with a specific focus on rare fusion subtypes, particularly ZC3H7B::BCOR, PHF1::TFE3 and MEAF6::PHF1. In addition, we included seven tumors with novel fusions, namely AFF3::PHF1, PHF1::KLF15, PHF1::PRKAG1, CREBBP::PHF1, EPC1::BMI1, MEAF6::BCOR, and EP300::BCORL1. The clinicopathological characteristics revealed a correlation between specific fusions and aggressive clinical behavior; notably, tumors with ZC3H7B::BCOR fusions were always classified as morphologically atypical or malignant and were associated with significantly higher recurrence and metastatic rates compared to other fusion groups, particularly EP400::PHF1. Immunohistochemical analysis further revealed a distinct immunophenotype in the ZC3H7B::BCOR group. While immunopositivity for cytokeratins and myogenic markers was observed in approximately one-quarter and more than one-third of OFMT cases overall, respectively, ZC3H7B::BCOR-rearranged tumors were negative for both. In contrast, the majority showed immunopositivity for pan-Trk. Additionally, DNA methylation profiling distinguished ZC3H7B::BCOR-rearranged cases from other fusion-positive OFMT, whereas the former clustered closely with a subset of high-grade endometrial stromal sarcomas. This study supports the recognition of ZC3H7B::BCOR-positive tumors as a distinct clinicopathological entity, contributing to the refined molecular taxonomy of this neoplasm. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3887 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3885 Recent survival trends in the most fatal cancers in the Nordic countries: gains in some but not in all Hemminki, Kari Jussi; Zitrický, František; Försti, Asta; Hemminki, Akseli Background Global survival studies distinguish a group of solid cancers with especially poor survival, which in the Nordic countries are cancers of the hypopharynx, esophagus, stomach, liver, gallbladder, pancreas, lung and pleura, each with a 5-year overall survival ranging between 15 to 30%. These cancers need extra attention. Methods We analyze here 1- and 5- year relative survival in the above cancers in Denmark, Finland, Norway and Sweden comparing periods 2013-18 and 2019-23 using the NORDCAN database. Results Survival improvement was significant for lung cancer in each country, more for women than for men. For females, 1- and 5-year lung cancer survival improvements were about 5 and 6 % units between the two periods, compared to all cancer of 1.5 and 2 % units, respectively. Regarding other individual sites, Norway and Sweden demonstrated significant survival improvements in stomach cancer, and Norway also in pancreatic cancer. However, non-significant survival improvements were observed for most cancers. No positive evidence was found for esophageal cancer in Finland and gallbladder cancer in Norway. More significant improvements were found for 1- than for 5-year survival. Conclusions Survival in lung cancer increased in all countries well over improvements for all cancers. Survival increased also significantly for stomach and pancreatic cancers in some countries, and improvements were seen for other cancers. Although the results show success in fight against the most fatal cancers, continuous efforts are needed in early detection, facile clinical handling and novel therapeutics. However, for these fatal cancers primary prevention would be highly rewarding. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3885 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3884 High-risk lineages shape the resistome and virulome of multidrug-resistant Pseudomonas aeruginosa Novakova, Kristyna; Sukkar, Iva; Palkovičová, Jana; Fiserova, Katerina; Vagnerova, Iva; Pudova, Vendula; Kolar, Milan Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa strains remain a major threat in clinical settings, yet no contemporary genomic data are available from the Olomouc region, Czech Republic. We performed whole-genome sequencing of 157 MDR isolates obtained from 133 patients hospitalized at two tertiary-care hospitals in Olomouc between April 2020 and April 2024. The aim of this study was to delineate the clonal structure, resistance and virulence repertoires shaping the local epidemiology. Of the 157 isolates, 81 (51.6%) met XDR criteria, most commonly exhibiting susceptibility to colistin (37/81, 45.7%). Four dominant high-risk sequence types (STs) were identified: ST175 (n = 53), ST357 (n = 49), ST233 (n = 25), and ST235 (n = 11). ST357 comprised two phylogenetically and functionally distinct sublineages: a major cluster (43/49) carrying bla (IMP-7) and bla (OXA-2), and a smaller bla (VIM-2)-positive cluster (5/49) lacking bla (OXA-2), oprD, soxR, and the pvc operon, correlating with an XDR phenotype and reduced biofilm-associated virulence potential. All ST357 isolates carried the cytotoxic exoU gene. Both bla (IMP-7) and bla (VIM-2) were chromosomally encoded. ST175 isolates lacked acquired carbapenemase genes, except for a single bla (VIM-2)-positive isolate. This lineage carried the highest number of virulence genes, dominated by adherence- and biofilm-associated determinants together with the characteristic exoS (+)/exoT (+)/exoY (+) type III secretion system profile. All ST233 isolates carried bla (VIM-2) and exhibited an XDR phenotype, consistent with globally disseminated VIM-2 lineages. ST235 displayed the greatest diversity of carbapenemase genes, including bla (GES-14) (5/11), bla (GES-29) (1/11), and bla (VIM-1) (1/11). This represented the first identification of a bla (VIM-1)-positive ST235 isolate in Olomouc University Hospital, and, to our knowledge, the first documented occurrence of a VIM-1-producing ST235 strain in the Czech Republic. All ST235 isolates were exoU-positive. This study provides a recent whole-genome analysis of MDR/XDR P. aeruginosa in the Czech Republic, integrating resistome, virulome and molecular epidemiology. Our findings demonstrate that the local population is shaped by multiple high-risk lineages with distinct resistance-virulence profiles, underscoring their clinical relevance and the necessity of genomic surveillance to guide therapy and prevent hospital transmission. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3884 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3874 Clinicopathologic features of KRAS G12C-mutated non-small cell lung carcinomas:insights from 279 retrospective cases Bradová, Martina; Slavík, Petr; Vaněček, Tomáš; Martínek, Petr; Grossmann, Petr; Kormunda, Stanislav; Behenská, Kristýna; Svatoň, Martin; Pešek, Miloš; Jirásek, Tomáš; Špůrková, Zuzana; Hroudová, Petra; Mrázková, Hana; Hořavová, Barbora; Roubec, Jaromír; Baník, Martin; Mukenšnabl, Petr; Michal, Michal; Švajdler, Marián KRAS G12C-mutated non-small cell lung carcinoma (NSCLC), caused by a glycine-to-cysteine substitution at codon 12, is associated with poor prognosis and is now targetable with specific inhibitors. We retrospectively analyzed 279 KRAS G12C-mutated NSCLC cases (2017-2023) from our registry with available histologic, immunohistochemical, and molecular data. The cohort included 279 patients (125 females, 151 males; mean age 67 years, range 29-91). Most tumors were primary lung carcinomas (n = 229, 82%), while 45 (16%) were metastatic at presentation. Morphologic evaluation was available in 240 tumors: 37% showed solid squamous cell carcinoma (SCC)-like features, 61% rhabdoid/plasmacytoid morphology, and 17% sarcomatoid features. Adenocarcinoma-associated patterns were present in 67 cases, often mixed, and focal solid growth occurred in 77%. TTF1, Napsin A, and CK7 were positive in 86%, 87%, and 98%, respectively, whereas squamous markers were infrequent (p40/p63 7%, CK5/6 8%). PD-L1 expression was detected in 65%. Co-mutations most commonly involved TP53 (n = 27) and STK11 (n = 12); IDH1/2, PIK3CA, and CTNNB1 mutations occurred in four cases each, MET in two cases, and BRAF, FGFR2, FGFR3, and GNAS in one case each. Two gene fusions were identified (LRP12::NRG1, FGFR3::TACC3). Mean survival was 1.89 years, with one- and five-year survival rates of 54% and 25%. KRAS G12C-mutated NSCLC is clinically aggressive and frequently shows solid growth with rhabdoid, plasmacytoid, or SCC-like morphology, which may lead to misclassification and missed genetic testing. Immunohistochemistry and molecular profiling are essential for accurate classification and enabling targeted therapy. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3874 2026-01-01T00:00:00Z