title: Downregulation of fibroblast growth factor receptor 2 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.
authors: Division of Diagnostic Pathology, Nippon Medical School Hospital, Tokyo, Japan.
authors: Ryuji
authors: R
authors: Ohashi
authors: Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
authors: Yoko
authors: Y
authors: Matsuda
authors: Departments of Pathology and Integrative Oncological Pathology, Nippon Medical School, Tokyo, Japan.
authors: Toshiyuki
authors: T
authors: Ishiwata
authors: Departments of Pathology and Integrative Oncological Pathology, Nippon Medical School, Tokyo, Japan.
authors: Zenya
authors: Z
authors: Naito
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D005260:Female; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics* / Q000378:metabolism*; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D020033:Protein Isoforms; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2