Moderate-to-strong expression of FGFR3 and TP53 alterations in a subpopulation of choroid plexus tumors

Kirsi J. Granberg^1,2,3, Annina Raita^4,5, Birgitta Lehtinen^1,2, Aliisa M. Tiihonen^1,2, Juha Kesseli^1,2, Matti Annala^1,2, Alejandra Rodriguez-Martinez^1,2, Kristiina Nordfors^6,7, Wei Zhang⁸, Tapio Visakorpi^1,2,4, Matti Nykter^1,2,3 and Hannu Haapasalo<sup>4,5

1</sup>BioMediTech, 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: kirsi.granberg@gmail.com

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

DOI: 10.14670/HH-18-180