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 sufficient to predict FGFR inhibitor response in MPM cell lines.
Highlights
Malignant pleural mesothelioma (MPM) is a devastating malignancy arising from mesothelial cells lining the chest cavity
FGFR1 and FGFR2 Show Strong Staining in MPM Tissue
Staining for FGFR1–4 was performed in tumor tissue from 94 MPM patients and evaluated using a three-tier semi quantitative scoring system
Summary
Malignant pleural mesothelioma (MPM) is a devastating malignancy arising from mesothelial cells lining the chest cavity. Asbestos is the main causative agent for MPM but the latency period between exposure and MPM manifestation can be more than 40 years [1]. MPM is highly refractory to conventional therapies and the prognosis is generally poor with a median overall survival of little more than one year. Chemotherapy with cisplatin and pemetrexed yields a modest survival benefit, which can be slightly improved only in selected patients by addition of bevacizumab and combination with surgery and/or radiotherapy as additional treatment modalities [3]. Despite multiple clinical studies investigating targeted therapies in MPM, no effective new treatments have been identified in this area, while immunotherapy seems to be moderately effective in a subgroup of patients [3,4]
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