Cells with intense EGFR staining and a high nuclear to cytoplasmic ratio are specific for infiltrative glioma: a useful marker in neuropathological practice

• Published in: Neuro-oncology (Charlottesville, Va.) Vol. 15; no. 10; pp. 1278 - 1288
• Main Authors: Burel-Vandenbos, Fanny, Turchi, Laurent, Benchetrit, Maxime, Fontas, Eric, Pedeutour, Zoe, Rigau, Valérie, Almairac, Fabien, Ambrosetti, Damien, Michiels, Jean-François, Virolle, Thierry
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.10.2013
• Subjects: Adult; Basic and Translational Investigations; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Blotting, Western; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Cell Nucleus - metabolism; Child; Cytoplasm - metabolism; Female; Flow Cytometry; Fluorescent Antibody Technique; Glioma - genetics; Glioma - metabolism; Glioma - pathology; Humans; Immunoenzyme Techniques; In Situ Hybridization, Fluorescence; Male; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Retrospective Studies; Tumor Cells, Cultured; infiltrative gliomas; progenitors; gliosis; immunohistochemistry; glioblastomas; EGFR
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/not094

The differential diagnosis between infiltrative glioma (IG) and benign or curable glial lesions, such as gliosis, pilocytic astrocytoma, dysembryoplastic neuroepithelial tumor, ganglioglioma, or demyelinating disease, may be challenging for the pathologist because specific markers are lacking. Recently, we described a strong EGFR immunolabelling pattern in cells with a high nuclear to cytoplasmic ratio that enables the discrimination of low-grade IG from gliosis. The aim of this study was to extend our observation to high-grade glioma to assess whether EGFR expression pattern is of value in the discrimination of all IG from noninfiltrative glial lesions (NIG), including gliosis, benign tumors, and demyelinating disease. One hundred one IG and 58 NIG were compared for immunohistochemical expression of EGFR with use of an antibody that recognizes an epitope in the extracellular domain of both EGFRwt and EGFRvIII. Highly EGFR-positive cells with a high nuclear to cytoplasmic ratio were isolated and further characterized. Cells with intense EGFR staining and a high nuclear to cytoplasmic ratio were significantly associated with the diagnosis of IG (P < .0001). The sensitivity and specificity of this staining pattern for the diagnosis of IG were 95% and 100%, respectively. EGFR expression was independent of IDH1 mutations and EGFR amplification. Finally, we showed that these particular cells displayed the phenotype and properties of glial progenitors and coexpressed CXCR4, a marker of invasiveness. We demonstrate that cells with intense EGFR staining and a high nuclear to cytoplasmic ratio are specific criteria for the diagnosis of IG, irrespective of grade, histological subtype, and progression pathway, and their identification represents a tool to discriminate IG from benign or curable glial lesions.