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Iskalni niz: "avtor" (Thomas Klikovits) .

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1.
Comparative analysis of prognostic histopathologic parameters in subtypes of epithelioid pleural mesothelioma
Agnes Bilecz, Paul Stockhammer, Dirk Theegarten, Izidor Kern, Marko Jakopović, Miroslav Samaržija, Thomas Klikovits, Mir Alireza Hoda, Balazs Dome, Felicitas Oberndorfer, 2020

Povzetek: Malignant pleural mesothelioma (MPM) is a rare malignancy with a dismal prognosis. While the epithelioid type is associated with a more favourable outcome, additional factors are needed to further stratify prognosis and to identify patients who can benefit from multimodal treatment. As epithelioid MPM shows remarkable morphological variability, the prognostic role of the five defined morphologies, the impact of the nuclear grading system and the mitosis-necrosis score were investigated in this study. Methods and results: Tumour specimens of 192 patients with epithelioid MPM from five European centres were histologically subtype d. Nuclear grading and mitosis–necrosi s score were determined and correlated with clinicopathological parameters and overall survival (OS). Digital slides of 55 independent cases from The Cancer Genome Atlas (TCGA) database were evaluated for external validation. Histological subtypes were collapsed into three groups based on their overlapping survival curves. The tubulopapillary/microcystic group had a significantly longer OS than the solid/trabecular group (732 days versus 397 days, P = 0.0013). Pleomorphic tumours had the shortest OS (173 days). The solid/trabecular variants showed a significant association with high nuclear grade and mitosis – necrosis score. The mitosis–necrosis score was a robust and independent prognostic factor in our patient cohort. The prognos- tic significance of all three parameters was externally validated in the TCGA cohort. Patients with tubulopapillary or microcystic tumours showed a greater improvement in OS after receiving multimodal therapy than those with solid or trabecular tumours. Conclusions: Histological subtypes of epithelioid MPM have a prognostic impact, and might help to select patients for intensive multimodal treatment approaches.
Ključne besede: epithelioid malignant pleural mesothelioma, histological subtypes
DiRROS - Objavljeno: 08.07.2020; Ogledov: 514; Prenosov: 192
URL Celotno besedilo (0,00 KB)

2.
Expression of FGFR1-4 in malignant pleural mesothelioma tissue and corresponding cell lines and its relationship to patient survival and FGFR inhibitor sensitivity
Gregor Vlačić, Mir Alireza Hoda, Thomas Klikovits, Katharina Sinn, Elisabeth Gschwandtner, Katja Mohorčič, Karin Schelch, Christine Pirker, Barbara Peter-Vörösmarty, Jelena Brankovic, Tanja Čufer, Aleš Rozman, Izidor Kern, 2019

Povzetek: Malignant pleural mesothelioma (MPM) is a devastating malignancy with limited therapeutic options. Fibroblast growth factor receptors (FGFR) and their ligands were shown to contribute to MPM aggressiveness and it was suggested that subgroups of MPM patients could benefit from FGFR-targeted inhibitors. In the current investigation, we determined the expression of all four FGFRs (FGFR1-FGFR4) by immunohistochemistry in tissue samples from 94 MPM patients. From 13 of these patients, we were able to establish stable cell lines, which were subjected to FGFR1-4 staining, transcript analysis by quantitative RT-PCR, and treatment with the FGFR inhibitor infigratinib. While FGFR1 and FGFR2 were widely expressed in MPM tissue and cell lines, FGFR3 and FGFR4 showed more restricted expression. FGFR1 and FGFR2 showed no correlation with clinicopathologic data or patient survival, but presence of FGFR3 in 42% and of FGFR4 in 7% of patients correlated with shorter overall survival. Immunostaining in cell lines was more homogenous than in the corresponding tissue samples. Neither transcript nor protein expression of FGFR1-4 correlated with response to infigratinib treatment in MPM cell lines. We conclude that FGFR3 and FGFR4, but not FGFR1 or FGFR2, have prognostic significance in MPM and that FGFR expression is not suffcient to predict FGFR inhibitor response in MPM cell lines.
Ključne besede: malignant pleural mesothelioma, fibroblast growth factor receptors, azbestos, immunotherapy, chemotherapy, genomic analysis, infigratinib
DiRROS - Objavljeno: 07.10.2020; Ogledov: 326; Prenosov: 152
URL Celotno besedilo (0,00 KB)

3.
Prognostic impact of PD-1 and PD-L1 expression in malignant pleural mesothelioma : an international multicenter study
Luka Brčić, Thomas Klikovits, Zsolt Megyesfalvi, Berta Mosleh, Katharina Sinn, Richard Hritcu, Viktoria Laszlo, Tanja Čufer, Aleš Rozman, Izidor Kern, Katja Mohorčič, 2021

Povzetek: Background: Programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) immune-checkpoint blockade is a promising new therapeutic strategy in cancer. However, expression patterns and prognostic significance of PD-L1 and PD-1 are still controversial in human malignant pleural mesothelioma (MPM). Methods: Formalin-fixed paraffin-embedded (FFPE) tumor samples from 203 MPM patients receiving standard treatment without immunotherapy were collected from 5 European centers. PD-L1 and PD-1 expression of tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) were measured by immunohistochemistry and correlated with clinical parameters and long-term outcome. Results: High (>10%) PD-L1 TC and PD-1 TILs expressions were found in 18 (8%) and 39 (24%) patients, respectively. PD-L1 was rarely expressed by TILs [>/=1%, n=13 (8%); >10%, n=1]. No significant associations were found between the PD-L1 or PD-1 expression of TCs or TILs and clinicopathological parameters such as stage or histological subtype. Notably, patients with high (>10%) TC-specific PD-L1 expression exhibited significantly worse median overall survival (OS) (6.3 vs. 15.1 months of those with low TC PD-L1 expression; HR: 2.51, P<0.001). In multivariate cox regression analysis adjusted for clinical parameters, high TC PD-L1 expression (>10%) proved to be an independent negative prognostic factor for OS (HR: 2.486, P=0.005). There was no significant correlation between PD-L1 or PD-1 expression of TILs and OS. Conclusions: In this multicenter cohort study, we demonstrate that high (>10%) PD-L1 expression of TCs independently predicts worse OS in MPM. Further studies are warranted to investigate the value of PD-L1/PD-1 expression as a marker for treatment response in MPM patients receiving immunotherapy.
Ključne besede: mesothelioma - anatomy and histology - analysis, 1malignant pleural mesothelioma, programmed death-ligand 1, programmed cell death 1, PD-L1
DiRROS - Objavljeno: 31.03.2021; Ogledov: 75; Prenosov: 33

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