Frequency and feasibility of detecting FGFR mRNA expression in archival samples of patients with cholangiocarcinoma (CCA)
| Autor: | Lipika Goyal, Andrew X. Zhu, David T. Ting, Jochen K. Lennerz, Vikram Deshpande, Nabeel Bardeesy, Abhijit Chougule |
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| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 37:281-281 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 281 Background: Fibroblast growth factor receptor (FGFR) inhibitors show promising activity in patients with intrahepatic CCA harboring FGFR2 fusions, but these alterations have a modest frequency of 15-20%. FGFR mRNA expression has shown preliminary potential as a predictive biomarker for FGFR inhibition in advanced urothelial cancer and is currently being used for patient selection in clinical trials. To assess if we can increase the number of patients with CCA eligible for FGFR inhibitor trials, we evaluated the frequency and feasibility of detecting FGFR mRNA overexpression in archival CCA tissue. Methods: Patients with intrahepatic and extrahepatic CCA who received treatment at the MGH between 1/2004 and 12/2013 were included. Tissue microarrays of archival specimens were stained using the FGFR1-3 pooled, FGFR1, and FGFR2 RNA in situ hybridization probes (RNAscope 2.5 assay). Clinicopathologic data were obtained from the medical record. CCA cell lines were assessed for sensitivity to the FGFR selective inhibitor BGJ398 and also for FGFR expression by qPCR. Results: 90/111 (81%) TMA specimens were evaluable: median age 62.6 years, female 63%, median tumor size 5.1cm, intrahepatic/extrahepatic 71%/29%%. Among the 90 samples, 14% samples stained negative for the pooled FGFR1-3 probe, and 23%, 32%, and 30% stained 1+, 2+, and 3+ positive, respectively. Of note, majority of the samples stained 3+ for FGFR2. Examination of 11 ICC cell lines lacking FGFR gene abnormalities revealed that the single line with marked overexpression of FGFR1 exhibited hypersensitivity to BGJ398. Conclusions: Selection of patients with CCA for treatment with FGFR inhibitors based on mRNA expression levels is feasible on archival tissue with the FGFR RNA ISH probes, and this technique may identify a subpopulation of patients without FGFR genetic abnormalities who may benefit from FGFR inhibitors. [Table: see text] |
| Databáze: | OpenAIRE |
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