Assessment of Epidermal Growth Factor Receptor (EGFR) expression in human meningioma

<p>Abstract</p> <p>Purpose</p> <p>This study explores whether meningioma expresses epidermal growth factor receptor (EGFR) and determines if there is a correlation between the WHO grade of this tumor and the degree of EGFR expression.</p> <p>Methods</p> <p>Following institutional review board approval, 113 meningioma specimens from 89 patients were chosen. Of these, 85 were used for final analysis. After a blinded review, immunohistochemical stains for EGFR were performed. Staining intensity (SI) was scored on a scale 0-3 (from no staining to strong staining). Staining percentage of immunoreactive cells (SP) was scored 1-5 (from the least to the maximum percent of the specimen staining). Immunohistochemical score (IHS) was calculated as the product of SI and SP.</p> <p>Results</p> <p>Eighty-five samples of meningioma were classified in accordance with World Health Organization (WHO) criteria: benign 57/85 (67%), atypical 23/85 (27%), and malignant 5/85 (6%). The majority of samples demonstrated a moderate SI for EGFR. IHS for EGFR demonstrated a significant association between SI and histopathologic subtype. Also, there was a correlation between the SP and histopathologic subtype (p = 0.029). A significant association was determined when the benign and the atypical samples were compared to the malignant with respect to the SP (p = 0.009). While there was a range of the IHS for the benign and the atypical histologic subtypes, malignant tumors exhibited the lowest score and were statistically different from the benign and the atypical specimens (p < 0.001).</p> <p>Conclusions</p> <p>To our knowledge, this represents the largest series of meningioma samples analyzed for EGFR expression reported in the literature. EGFR expression is greatest in benign meningiomas and may serve a potential target for therapeutic intervention with selective EGFR inhibitors.</p

Clinical significance of <i>EGFR</i> amplification and the aberrant EGFRVIII transcript in conventionally treated astrocytic gliomas

The aim of this study was to evaluate the clinical value of assessing EGFR amplification, and the common 5′ rearrangement of EGFR resulting in the EGFRvIII transcript in astrocytic gliomas. The data from 221 tumours was correlated with patient survival. The majority of previous studies evaluated amplification alone and have provided contradictory results. Amplification was analyzed by densitometry of Southern blots or quantitative PCR. EGFR transcripts were examined by RT-PCR and subsequent sequencing. An RNase protection assay was carried out on a subgroup to confirm the PCR results. Amplification of EGFR was found in 41% (65/160) of glioblastomas (GB), and 10% (4/41) of anaplastic astrocytomas (AA). The EGFRvIII rearrangement was identified in 54% (35/65) of GB and 75% (3/4) of AA with amplification as well as in 8% (8/95) of GB and 5% (2/37) of AA without amplification (confirmed by RNase protection essay). There were no abnormalities of the EFGR or its transcript in astrocytomas malignancy grade II (AII). We found no significant association between EGFR amplification or rearrangement and age or survival in the 160 GB patients. We noted a tendency towards decreased survival in the 41 patients with AA with any EGFR abnormality. This was most marked in the 5 cases with the EGFRvIII transcript (p=0,069) but these were significantly older than those without (p=0,023). No abnormalities of EGFR were identified in AII patients. We conclude that neither EGFR amplification nor the presence of the EGFRvIII transcript predict patient outcome in conventionally treated GB. In AA however, although uncommon, EGFR aberrations appear to be associated with shorter survival