Downregulation of fibroblast growth factor receptor 2 and its isoforms correlates with a high proliferation rate and poor prognosis in high-grade glioma

Ohashi,Ryuji; Matsuda,Yoko; Ishiwata,Toshiyuki; Naito,Zenya

doi:10.3892/or.2014.3283

Downregulation of fibroblast growth factor receptor 2 and its isoforms correlates with a high proliferation rate and poor prognosis in high-grade glioma

Authors:
- Ryuji Ohashi
- Yoko Matsuda
- Toshiyuki Ishiwata
- Zenya Naito
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Affiliations: Division of Diagnostic Pathology, Nippon Medical School Hospital, Tokyo, Japan, Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan, Departments of Pathology and Integrative Oncological Pathology, Nippon Medical School, Tokyo, Japan
Published online on: June 23, 2014 https://doi.org/10.3892/or.2014.3283
Pages: 1163-1169

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Abstract

Fibroblast growth factor receptor 2 (FGFR-2) contributes to the progression of numerous types of cancers; however, its role in glioma has yet to be determined. We investigated the expression of FGFR-2 and its predominant isoforms, FGFR-2 IIIb and FGFR-2 IIIc, in gliomas of all histological grades. Using immunohistochemistry, we demonstrated that FGFR-2, FGFR-2 IIIb and FGFR-2 IIIc were expressed in the astrocytes of normal human brains. The percentages of cells expressing FGFR-2, FGFR-2 IIIb and FGFR-2 IIIc and the intensities of their staining in glioblastomas (grade IV) were significantly reduced when compared to these parameters in the low-grade tumors (grade I, II and III; P<0.05). A high MIB-1 index, indicated by Ki-67 expression in >20% of the cells, was also associated with low expression of each FGFR-2 protein. Lower expression of FGFR-2 and FGFR-2 IIIc was correlated with a reduced survival rate (P=0.02 and 0.0253, respectively). Quantitative PCR analysis confirmed that the mRNA levels of FGFR-2 IIIb and FGFR-2 IIIc in a high-grade glioma-derived cell line (YKG-1) were lower than levels in a low-grade glioma-derived cell line (KG-1-C). These findings suggest that the decrease or loss of FGFR-2, FGFR-2 IIIb and FGFR-2 III in high-grade gliomas correlates with poor prognosis, which we attribute to the high proliferation rate of the tumor.

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