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Iskalni niz: "avtor" (Gregor Vlačić) .

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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: 324; Prenosov: 149
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Reproducibility of malignant pleural mesothelioma histopathologic subtyping
Luka Brčić, Gregor Vlačić, Franz Quehenberger, Izidor Kern, 2018

Povzetek: Context. Malignant pleural mesothelioma (MPM) is a rare tumor with poor prognosis. Several studies have analyzed potential prognostic markers, but histologic type remains the single most important prognostic factor. Histologic subtypes of epithelioid MPM seem to have prognostic and therapeutic implications. Interobserver agreement in histologic pattern classification should be high. Objective. To assess interobserver and intraobserver reproducibility in histologic differentiation between the main types of MPMs, and in further subtyping of epithelioid-type mesothelioma. Design. One representative hematoxylin-eosin-stained slide was selected from the archive for each of 200 patients with MPM. They were reviewed independently by 3 pathologists and classified according to the current World Health Organization classification of pleural tumors. After the first round of evaluations, a consensus meeting was organized where problems were addressed and representative images for each histologic category were selected. Two months later, cases were reevaluated by all 3 pathologists. Results. After the first round, overall interobserver agreement for histologic subtyping of mesothelioma was fair (k, 0.36). The agreement was increased to substantial (k, 0.63) in the second round. Improvement was found in interobserver agreement for all types of MPM, and for most epithelioid subtypes. Conclusions. Moderate to substantial agreement in histologic typing and subtyping of MPM can be achieved. However, training with additional clarification of diagnostic criteria, their strict application, and help from consensus-based illustrative images is needed.
Ključne besede: connective and soft tissue neoplasms -- pathology, malignant pleural mesothelioma, histopathology
DiRROS - Objavljeno: 30.11.2020; Ogledov: 222; Prenosov: 56

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