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

Histopathology. 2016 Aug;69(2):329-37. doi: 10.1111/his.12944. Epub 2016 Mar 21.

Abstract

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).

Keywords: Cav1; YKL-40; c-Met; granular-cell astrocytoma; granular-cell glioblastoma.

MeSH terms

  • Adult
  • Aged
  • Astrocytoma / classification*
  • Astrocytoma / diagnosis
  • Astrocytoma / genetics
  • Astrocytoma / pathology
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Brain Neoplasms / classification*
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Caveolin 1 / genetics
  • Caveolin 1 / metabolism*
  • Chitinase-3-Like Protein 1 / genetics
  • Chitinase-3-Like Protein 1 / metabolism*
  • Cohort Studies
  • Female
  • Glioblastoma / classification
  • Glioblastoma / diagnosis
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Granular Cell Tumor / classification
  • Granular Cell Tumor / diagnosis
  • Granular Cell Tumor / genetics
  • Granular Cell Tumor / pathology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins c-met / metabolism*

Substances

  • Biomarkers, Tumor
  • CAV1 protein, human
  • CHI3L1 protein, human
  • Caveolin 1
  • Chitinase-3-Like Protein 1
  • Proto-Oncogene Proteins c-met

Associated data

  • GENBANK/NM_000314
  • GENBANK/NM_000546
  • GENBANK/NM_000619
  • GENBANK/NM_002168
  • GENBANK/NM_004333
  • GENBANK/NM_005228
  • GENBANK/NM_005896