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Query: "author" (Katharina Sinn) .

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1.
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

Abstract: 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.
Keywords: malignant pleural mesothelioma, fibroblast growth factor receptors, azbestos, immunotherapy, chemotherapy, genomic analysis, infigratinib
DiRROS - Published: 07.10.2020; Views: 11427; Downloads: 466
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2.
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

Abstract: 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.
Keywords: mesothelioma - anatomy and histology - analysis, 1malignant pleural mesothelioma, programmed death-ligand 1, programmed cell death 1, PD-L1
DiRROS - Published: 31.03.2021; Views: 601; Downloads: 301

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