Downregulation of fibroblast growth factor receptor2 and its isoforms correlates with a high proliferation rate and poor prognosis in high-grade glioma.

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.