Moderate-to-strong expression of FGFR3 and TP53 alterations in a subpopulation of choroid plexus tumors
Kirsi J. Granberg1,2,3, Annina Raita4,5, Birgitta Lehtinen1,2, Aliisa M. Tiihonen1,2, Juha Kesseli1,2, Matti Annala1,2, Alejandra Rodriguez-Martinez1,2, Kristiina Nordfors6,7, Wei Zhang8, Tapio Visakorpi1,2,4, Matti Nykter1,2,3 and Hannu Haapasalo4,5
1BioMediTech, Faculty of Medicine and Health Technology, Tampere University, 2Tays Cancer Center, Tampere University Hospital, 3Science Center, Tampere University Hospital, 4Fimlab Laboratories Ltd., Tampere University Hospital, 5Department of Pathology, Tampere University, 6Department of Pediatrics, Tampere University Hospital, 7Tampere Center for Child Health Research, Tampere University, Tampere, Finland and 8Department of Cancer Biology, Wake Forest Baptist Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, NC USA
Offprint requests to: Kirsi J. Granberg, Faculty of Medicine and Health Technology, Arvo Ylpön katu 34, P.O. Box 100, FI-33014 Tampere University, Tampere, Finland. e-mail: firstname.lastname@example.org
Summary. Deregulation of fibroblast growth factor receptor (FGFR) signaling is tightly associated with numerous human malignancies, including cancer. Indeed, FGFR inhibitors are being tested as anti-tumor drugs in clinical trials. Among gliomas, FGFR3 fusions occur in IDH wild-type diffuse gliomas leading to high FGFR3 protein expression and both, FGFR3 and FGFR1, show elevated expression in aggressive ependymomas. The aim of this study was to uncover the expression of FGFR1 and FGFR3 proteins in choroid plexus tumors and to further characterize FGFR-related as well as other genetic alterations in FGFR3 expressing tumors.
Expression levels of FGFR1 and FGFR3 were detected in 15 choroid plexus tumor tissues using immunohistochemistry of tissue microarrays and 6 samples were subjected to whole mount FGFR3 staining. Targeted sequencing was used for deeper molecular analysis of two FGFR3 positive cases.
Moderate expression of FGFR1 or FGFR3 was evidenced in one third of the studied choroid plexus tumors. Targeted sequencing of a choroid plexus carcinoma and an atypical choroid plexus papilloma, both with moderate-to-strong FGFR3 expression, revealed lack of protein-altering mutations or fusions in FGFR1 or FGFR3, but TP53 was altered in both tumors.
FGFR3 and FGFR1 proteins are expressed in a subpopulation of choroid plexus tumors. Further studies using larger cohorts of patients will allow identification of the clinicopathological implications of FGFR1 and FGFR3 expression in choroid plexus tumors. Histol Histopathol 35, 673-680 (2020)
Key words: Tissue microarray, Deep-sequencing, FGFR gene fusion, Immunohistochemical staining, Brain tumor