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2. Association of tumor-infiltrating lymphocytes and inflammation status with survival outcome in patients with high-grade serous ovarian carcinomaSimona Miceska, Cvetka Grašič-Kuhar, Snježana Frković-Grazio, Erik Škof, Praveen Krishnamoorthy, Dineo Khabele, Veronika Kloboves-Prevodnik, 2025, izvirni znanstveni članek Povzetek: In this study, we investigated the association between tumor-infiltrating lymphocytes (TILs), inflammation status, and progression-free survival (PFS) in patients with primary high-grade serous ovarian carcinoma (HGSC). We assessed the percentages of different intraepithelial and stromal TIL subtypes using both manual and digital methods, following established recommendations for TIL assessment. In addition, we evaluated inflammation status through several immune scores, including the pan-immune-inflammation value (PIV). Our results suggest that stromal CD3+ and CD8+ TILs, as well as PIV, may serve as potential prognostic indicators in HGSC, as they remained potential independent markers in multivariate analysis.
Ključne besede: ovarian carcinoma, high-grade serous ovarian carcinoma, prognostic factors
Objavljeno v DiRROS: 05.12.2025; Ogledov: 786; Prenosov: 77
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3. Complementary detection strategies for circulating tumor cells in breast cancer: clinical implications of combining immunofluorescence and cytopathological stainingTanja Jesenko, Cvetka Grašič-Kuhar, Živa Pišljar, Simona Miceska, Veronika Kloboves-Prevodnik, Maja Čemažar, 2025, izvirni znanstveni članek Povzetek: Background: Circulating Tumor Cells (CTCs) serve as important biomarkers for disease monitoring and treatment response in patients with metastatic breast cancer. Their detection remains challenging because of their low abundance, phenotypic diversity and non-standardized mode of detection. Cytopathological Giemsa and Immunofluorescence (IF) staining can offer complementary approaches for CTC characterization. Giemsa staining enables assessment of cellular morphology, while IF allows for marker-specific identification, together providing a more comprehensive and accurate evaluation of CTCs. Methods: We developed an IF staining protocol with antibodies against Cytokeratin (CK), vimentin (VIM), and Cluster of Differentiation 45 (CD45) to distinguish epithelial, mesenchymal, hybrid and hematopoietic cells for CTC detection and characterization and compared it with cytopathologic method of detection via Giemsa staining with regard to CTC detection rates and morphological detail. Results: Study was performed on the samples of 29 heavily pretreated patients with metastatic breast cancer (median duration of metastatic disease 19.4 months). Giemsa staining enabled the detection of a higher number of CTCs compared to our IF protocol. Lower detection rate was potentially due to the loss of fragile or loosely adherent cells during methanol fixation and IF staining. Additionally, in IF-stained samples, some CTCs presented faint nuclear signals, potentially impairing their recognition. The IF staining supported the identity of CTCs detected on Giemsa-stained slides by employing a three-color antibody panel-based approach and allowed detailed phenotypic discrimination and structural analysis of CTCs, including the identification of a distinctive CK polarization pattern suggestive of a transitional state during intravasation. Conclusion: Giemsa and IF may thus be complementary rather than mutually exclusive and relying on a single detection approach could underestimate the true CTC burden. An integrative strategy combining both techniques may offer a more comprehensive view of CTC populations in metastatic breast cancer, thereby enhancing diagnostic precision.
Ključne besede: biomarkers, breast cancer, circulating tumor cells, cytopathological detection
Objavljeno v DiRROS: 05.12.2025; Ogledov: 884; Prenosov: 74
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4. Diagnosis of pediatric myositis ossificans based on cytomorphology and molecular analysis from FNAB sample : a case reportŽiva Ledinek, Milica Stefanović, Blaž Mavčič, Maja Česen, Ana Gazikalović, Daja Šekoranja, Simona Miceska, Veronika Kloboves-Prevodnik, 2025, drugi znanstveni članki Ključne besede: USP6 gene, case report, pediatric diagnosis
Objavljeno v DiRROS: 21.11.2025; Ogledov: 213; Prenosov: 131
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5. Plevralni, abdominalni in perikardialni limfocitni izlivVeronika Kloboves-Prevodnik, Živa Ledinek, Aleš Rode, Gorana Gašljević, 2025, strokovni članek Povzetek: Limfocitni izliv je zaplet različnih bolezni. Malignomi in tuberkuloza sta najpogostejši vzrok za večino limfocitnih izlivov. Limfociti v izlivu so lahko reaktivni ali neoplastični. Reaktivni limfocitni izliv nastane zaradi vnetij, sistemskih ali avtoimunskih bolezni, karcinoze ali drugih redkih vzrokov. Maligni limfocitni izliv najpogosteje nastane pri bolnikih z napredovalimi nodalnimi in ekstranodalnimi limfomi, ki so se razširili v plevralni, perikardialni ali abdominalni prostor. Zelo redko nastane zaradi limfomov, ki vzniknejo na seroznih površinah. Diagnozo limfoma v izlivu postavimo na podlagi kliničnih podatkov, mikroskopske slike in dodatnih imunofenotipskih ter molekularnih preiskav. V skladu z mednarodnimi smernicami limfoproliferativne bolezni v izlivih razdelimo v pet diagnostičnih kategorij: nediagnostično, benigno, atipične celice neopredeljene, sumljivo za malignom in maligno.
Ključne besede: limfocitni izliv, limfom, citopatološka diagnostika
Objavljeno v DiRROS: 18.07.2025; Ogledov: 458; Prenosov: 154
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6. Razvoj raziskav cirkulirajočih tumorskih celic pri raku dojk na Onkološkem inštitutu LjubljanaTanja Jesenko, Cvetka Grašič-Kuhar, Živa Pišljar, Simona Miceska, Veronika Kloboves-Prevodnik, Maja Čemažar, 2024, pregledni znanstveni članek Povzetek: Cirkulirajoče tumorske celice (CTC) so postale pomemben biološki označevalec pri raku dojk, saj omogočajo vpogled v razvoj in napredovanje razsejane bolezni ter spremljanje odziva na zdravljenje. Zaradi njihove izjemne redkosti in kompleksnosti sestave krvi, v kateri se nahajajo, sta njihova izolacija in karakterizacija velik izziv. Posebne metode izolacije omogočajo obogatitev CTC iz vzorca krvi in olajšajo nadaljnjo analizo. Na Onkološkem inštitutu Ljubljana smo leta 2018 začeli s prvimi koraki v smeri razvoja preproste metode za izolacijo in karakterizacijo CTC, ki bi omogočala prepoznavanje teh celic s citopatološkimi analizami. Ocenili smo dve različni metodi izolacije CTC pri bolnicah z rakom dojk, ki temeljita na različnih pristopih. Prva metoda temelji na bioloških lastnostih celic, kot je izražanje epitelijskega označevalca celične adhezije (EpCAM), medtem ko druga metoda temelji na fizikalnih lastnostih CTC, kot sta večja velikost in stisljivost v primerjavi z drugimi krvnimi celicami. Ugotovili smo, da je fizikalna metoda primernejša, saj omogoča izolacijo večjega števila morfološko ohranjenih CTC in tudi skupkov CTC. Po izolaciji pripravimo citološke preparate, ki jih nato opredelimo s citopatološko analizo in dodatnimi imunocitokemičnimi ter imunofluorescenčnimi barvanji. Na ta način lahko trenutno določimo število CTC in skupkov CTC v krvi, ocenimo njihovo morfološko ohranjenost ter prepoznamo njihov fenotip. Poleg preučevanja vzorcev posamičnih CTC in skupkov CTC v okviru trenutno potekajočih kliničnih raziskav in načrtovane vzpostavitve translacijske platforme na mišjih modelih, pa v prihodnosti želimo nabor raziskav CTC še razširiti na genomsko in transkriptomsko analizo.
Ključne besede: cirkulirajoče tumorske celice, rak dojk, eksperimentalna onkologija
Objavljeno v DiRROS: 21.05.2025; Ogledov: 595; Prenosov: 201
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8. FoxP3+ regulatory T-cell quantities in nodal T-follicular helper cell lymphomas and peripheral T-cell lymphomas not otherwise specified and their impact on overall survivalEva Erzar, Alexandar Tzankov, Janja Ocvirk, Biljana Grčar-Kuzmanov, Lučka Boltežar, Veronika Kloboves-Prevodnik, Gorana Gašljević, 2024, izvirni znanstveni članek Povzetek: The role of FoxP3+ regulatory T cells (Tregs) in the tumour microenvironment (TME) of peripheral T-cell lymphomas (PTCLs) is complex, and their impact on overall survival (OS) is unclear. This retrospective study aims to examine the quantity of FoxP3+ cells in the TME of PTCLs and reactive lymph nodes (LNs) and their impact on OS. A lower FoxP3+ cell quantity is found in PTCLs compared to reactive LNs. While differences in OS are observed between groups with high and low FoxP3+ cell quantities using various cut-off values, further analyses show no significant impact on the risk of death. This study suggests FoxP3+ cells as potential prognostic biomarkers but recommends the conduction of larger, multicentre studies with standardized protocols for confirmation. It also indicates that Treg-suppressing drugs may not be suitable for certain PTCL patients. Instead, combining therapies, including those enhancing Treg function, could be more effective in improving outcomes for PTCL patients, warranting further research.
Ključne besede: lymphoma, prognostic biomarkers, overall survival
Objavljeno v DiRROS: 09.01.2025; Ogledov: 1198; Prenosov: 504
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9. The prognostic significance of tumor-immune microenvironment in ascites of patients with high-grade serous carcinomaSimona Miceska, Erik Škof, Simon Buček, Cvetka Grašič-Kuhar, Gorana Gašljević, Špela Smrkolj, Veronika Kloboves-Prevodnik, 2023, izvirni znanstveni članek Povzetek: Background: High-grade serous carcinoma (HGSC) is often associated with ascites at presentation. Our objective was to quantify immune cells (ICs) in ascites prior to any treatment was given and evaluate their impact on progression-free survival (PFS) and overall survival (OS). Patients and methods: Forty-seven patients with primary HGSC and ascites were included. Flow-cytometric analysis was performed to detect percentages of CD3+ T cells (CD4+, CD8+, Tregs, and NKT cells), B cells, NK cells (CD56brightCD16- and CD56dimCD16+ subsets), macrophages and dendritic cells (DCs). Furthermore, CD103 expression was analyzed on T cells and their subsets, while PD-1 and PD-L1 expression on all ICs. Cut-off of low and high percentages of ICs was determined by the median of variables, and correlation with PFS and OS was calculated. Results: CD3+ cells were the predominant ICs (median 51%), while the presence of other ICs was much lower (median ≤10%). CD103+ expression was mostly present on CD8+, and not CD4+ cells. PD-1 was mainly expressed on CD3+ T cells (median 20%), lower expression was observed on other ICs (median ≤10%). PD-L1 expression was not detected. High percentages of CD103+CD3+ T cells, PD-1+ Tregs, CD56brightCD16- NK cells, and DCs correlated with prolonged PFS and OS, while high percentages of CD8+ cells, macrophages, and PD-1+CD56brightCD16- NK cells, along with low percentages of CD4+ cells, correlated with better OS only. DCs were the only independent prognostic marker among all ICs. Conclusions: Our results highlight the potential of ascites tumor-immune microenvironment to provide additional prognostic information for HGSC patients. However, a larger patient cohort and longer follow-up are needed to confirm our finBackground: High-grade serous carcinoma (HGSC) is often associated with ascites at presentation. Our objective was to quantify immune cells (ICs) in ascites prior to any treatment was given and evaluate their impact on progression-free survival (PFS) and overall survival (OS). Patients and methods: Forty-seven patients with primary HGSC and ascites were included. Flow-cytometric analysis was performed to detect percentages of CD3+ T cells (CD4+, CD8+, Tregs, and NKT cells), B cells, NK cells (CD56brightCD16- and CD56dimCD16+ subsets), macrophages and dendritic cells (DCs). Furthermore, CD103 expression was analyzed on T cells and their subsets, while PD-1 and PD-L1 expression on all ICs. Cut-off of low and high percentages of ICs was determined by the median of variables, and correlation with PFS and OS was calculated. Results: CD3+ cells were the predominant ICs (median 51%), while the presence of other ICs was much lower (median ≤10%). CD103+ expression was mostly present on CD8+, and not CD4+ cells. PD-1 was mainly expressed on CD3+ T cells (median 20%), lower expression was observed on other ICs (median ≤10%). PD-L1 expression was not detected. High percentages of CD103+CD3+ T cells, PD-1+ Tregs, CD56brightCD16- NK cells, and DCs correlated with prolonged PFS and OS, while high percentages of CD8+ cells, macrophages, and PD-1+CD56brightCD16- NK cells, along with low percentages of CD4+ cells, correlated with better OS only. DCs were the only independent prognostic marker among all ICs. Conclusions: Our results highlight the potential of ascites tumor-immune microenvironment to provide additional prognostic information for HGSC patients. However, a larger patient cohort and longer follow-up are needed to confirm our findings.dings.
Ključne besede: high-grade serous carcinoma, immune cells, prognostic markers
Objavljeno v DiRROS: 26.07.2024; Ogledov: 1800; Prenosov: 728
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10. CD56-positive diffuse large B-cell lymphoma : comprehensive analysis of clinical, pathological, and molecular characteristics with literature reviewGorana Gašljević, Lučka Boltežar, Srdjan Novaković, Vita Šetrajčič Dragoš, Barbara Jezeršek Novaković, Veronika Kloboves-Prevodnik, 2023, izvirni znanstveni članek Povzetek: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. The expression of CD56 in DLBCL is highly unusual. Little is known about its incidence and clinical importance. So far, no genetic profiling was performed in CD56 positive DLBCL.Patients and methods. Tissue microarrays have been constructed, sectioned, and stained by H&E and immuno-histochemistry for 229 patients with DLBCL diagnosed 2008–2017. For CD56 positive cases, clinical data was collected including age at diagnosis, stage of the disease, International Prognostic Index (IPI) score, treatment scheme and number of chemotherapy cycles, radiation therapy, treatment outcome, and possible relapse of the disease. Overall survival (OS) and progression-free survival (PFS) were calculated. For four patients, RNA was extracted and targeted RNA (cDNA) sequencing of 125 genes was performed with the Archer FusionPlex Lymphoma kit.Results. CD56 expression was found in 7 cases (3%). The intensity of expression varied from weak to moderate focal, to very intensive and diffuse. All patients had de novo DLBCL. The median age at the time of diagnosis was 54.5 years. Five of them were women and 2 males. According to the Hans algorithm, 6 patients had the germinal centre B cells (GBC) type and one non-GBC (activated B-cell [ABC]) type, double expressor. Genetic profiling of four patients ac-cording to Schmitz’s classification showed that 1 case was of the BN2 subtype, 1 of EZB subtype, 2 were unclassified. The six treated patients reached a complete response and did not experience progression of the disease during the median follow-up period of 80.5 months.Conclusions. We report on one of the largest series of CD56+DLBCL with detailed clinicopathological data and for the first time described genetical findings in a limited number of patients. Our results show that CD56 expression is rare, but seems to be present in prognostic favourable subtypes of DLBCL not otherwise specified (NOS) as tested by immunohistochemical or genetic profiling
Ključne besede: diffuse large B-cell lymphoma, immunohistochemistry, lymphomas, CD56
Objavljeno v DiRROS: 25.07.2024; Ogledov: 1056; Prenosov: 381
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