gms | German Medical Science

Objective: Fibroblast growth factors and their corresponding receptors are known to play a pivotal role in angiogenesis, proliferation and migration not only in terms of embryogenesis but also in malignant processes. Regarding gliomas, FGFs and their receptors are targets of non-specific therapies like tyrosin-kinase inhibitors but only little is known about the particular specific roles of the 18 known isoforms. Recently the FGF8 subfamily including splicing variants FGF17 and FGF18 came in focus of interest as a prognostic and therapeutic biomarker of ovarian cancer. This prompted us to analyze the expression levels of the FGF8 subfamily in gliomas of different tumor grades aiming to detect the role of these factors in gliomagenesis.

Method: cDNA was synthesized from mRNA of 51 snap frozen tumor samples from patients with gliomas of different tumor grades (WHO grade II, III, secondary glioblastoma, primary glioblastoma, peritumoral tissue). Using quantitative real-time PCR relative expression levels of several FGFs were analyzed. Quantitative data were normalized in relation to the housekeeping gene SDHA. Results are depicted in mean ± SEM. Results were correlated with clinical data from the medical records.

Results: Both FGF17 and FGF18 were markedly expressed in gliomas of all tested WHO grades. Whereas expression levels of FGF 17 hardly changed with malignant progression (WHO grade II: 13.5 ± 3.0; WHO grade III: 11.5 ± 7.0; WHO grade IV 13.7 ± 2.6), a significant increase of FGF18 was found in secondary glioblastomas compared to grade II and grade III tumors (p = 0.01). Preliminary results indicate a relation with clinical data (e.g. patient survival).

Conclusions: First data indicate that the FGF isoform 18 plays a role in malignant progression of glioma, being higher expressed with increasing tumor grade. Currently, we investigate this finding more deeply using functional assays in vitro.