Expression of FGFR1–4 in Malignant Pleural Mesothelioma Tissue and Corresponding Cell Lines and its Relationship to Patient Survival and FGFR Inhibitor Sensitivity

Autor: Tanja Cufer, Ales Rozman, Balazs Hegedus, Izidor Kern, Katharina Sinn, Viktoria Laszlo, Thomas Klikovits, Bettina Grasl-Kraupp, Barbara Peter-Vörösmarty, Katja Mohorcic, Gregor Vlacic, Christine Pirker, Michael Grusch, Elisabeth Gschwandtner, Mir Alireza Hoda, Walter Klepetko, Balazs Dome, Walter Berger, Karin Schelch, Jelena Brankovic
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
Mesothelioma
infigratinib sensitivity
Lung Neoplasms
Medizin
chemotherapy
0302 clinical medicine
lcsh:QH301-705.5
0303 health sciences
receptorji za fibroblastne rastne dejavnike
azbest
FGFR
imunoterapija
genomska analiza
General Medicine
Middle Aged
3. Good health
Fibroblast growth factor receptor
fibroblast growth factor receptors
030220 oncology & carcinogenesis
embryonic structures
immunohistochemistry
Immunohistochemistry
Female
immunotherapy
musculoskeletal diseases
overall survival
Antineoplastic Agents
Malignancy
Article
infigratinib
03 medical and health sciences
Cell Line
Tumor
medicine
Humans
Receptor
Fibroblast Growth Factor
Type 3
malignant pleural mesothelioma
Receptor
Fibroblast Growth Factor
Type 4
Receptor
Fibroblast Growth Factor
Type 1
Receptor
Fibroblast Growth Factor
Type 2
Protein Kinase Inhibitors
030304 developmental biology
udc:616-006
Acrylamides
Dose-Response Relationship
Drug
business.industry
kemoterapija
Fibroblast growth factor receptor 1
Gene Expression Profiling
Phenylurea Compounds
Mesothelioma
Malignant
Fibroblast growth factor receptor 4
medicine.disease
Survival Analysis
Staining
azbestos
stomatognathic diseases
Pyrimidines
lcsh:Biology (General)
genomic analysis
Cell culture
Cancer research
Quinazolines
maligni plevralni mezoteliom
business
Immunostaining
Zdroj: Cells, Vol 8, Iss 9, p 1091 (2019)
Cells
Volume 8
Issue 9
Cells, vol. 8, no. 9, pp. 1-14, 2019.
ISSN: 2073-4409
Popis: 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&ndash
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&ndash
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&ndash
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 sufficient to predict FGFR inhibitor response in MPM cell lines.
Databáze: OpenAIRE
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