Mesenchymal/radioresistant traits in granular astrocytomas: evidence from a combined clinical and molecular approach

Aims: Granular-cell astrocytomas (GCAs) are morphologically characterized by a prominent component of granular periodic acid–Schiff-positive cells, and show increased aggressiveness as compared with ‘ordinary’ astrocytomas. The aim of this study was to investigate, in a small series of three GCAs, the expression of mesenchymal/radioresistance-associated biomarkers [such as chitinase-3-like protein 1 (YKL-40), hepatocyte growth factor receptor (c-Met), and caveolin 1 (Cav1)] that could contribute to the poor outcome associated with this glioma subgroup. Methods and results: Our results show that GCAs, according to the new molecular glioma classifications, consistently show a prognostically negative molecular trait (IDH1wt-ATRX noloss-1p/19q nocodeletion). Furthermore, GCAs significantly differed from a control series of 33 ‘conventional’ astrocytomas, because of diffuse and strong immunohistochemical coexpression of YKL-40, c-Met, and Cav1. Conclusions: Our findings show that specific morphological traits, such as a granular-cell component, could represent useful features in guiding the search for prognostic and predictive biomarkers that could eventually be therapy-targetable (e.g. Met inhibitors aimed at reducing radioresistance).