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Year : 2016  |  Volume : 64  |  Issue : 1  |  Page : 27--28

Epidermal growth factor receptor (EGFR) gene amplification in high grade gliomas

Chitra Sarkar 
 Department of Pathology, All Institute of Medical Sciences, New Delhi, India

Correspondence Address:
Chitra Sarkar
Department of Pathology, All India Institute of Medical Sciences, New Delhi

How to cite this article:
Sarkar C. Epidermal growth factor receptor (EGFR) gene amplification in high grade gliomas.Neurol India 2016;64:27-28

How to cite this URL:
Sarkar C. Epidermal growth factor receptor (EGFR) gene amplification in high grade gliomas. Neurol India [serial online] 2016 [cited 2021 Oct 16 ];64:27-28
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The authors evaluated the frequency of EGFR gene amplification in high grade gliomas (HGG) by fluorescence in-situ hybridization (FISH) and correlated it with various clinicopathological parameters. Remarkably, it is the largest series from India studied for EGFR amplification (n = 324). Not surprisingly, the authors found the highest frequency of EGFR amplification in adult glioblastomas [GBMs] (34%). The EGFR amplification was completely absent in pediatric GBMs as well as grade III anaplastic astrocytic and oligodendroglial tumours, and rare in cases of gliosarcoma and anaplastic oligoastrocytoma. These findings are predominantly confirmatory of the previously reported literature from India as well as from Western countries.[1],[2] Overall GBMs in children have a genetic and epigenetic profile distinct from that in GBMs of adult patients which is further supported by this study.[1],[3],[4]

Interestingly, the authors found EGFR amplification in approximately one third of cases of GBM with oligodendroglioma component (GBM-O); however, none of the cases had 1p/19q co-deletion. Although considered as a distinct subset of GBM, these tumours are pathogenetically heterogeneous and show a wide variability in the frequency of various molecular alterations (IDH1 mutations – 19 to 38%; 1p/19q co-deletion – 4% to 30%; EGFR amplification – 23 to 71%), which may possibly be attributable to the subjectivity and lack of uniformity in the parameters defined for the diagnosis of GBM-O. Further, there are morphological mimickers of GBM-O such as anaplastic oligodendroglioma, anaplastic oligoastrocytoma and small cell GBM.[5],[6],[7] Hence, the upcoming updated WHO classification proposes not to consider GBM-O as a separate diagnostic entity but suggests that these cases should be classified on the basis of IDH and 1p/19q status into: (i) GBM, IDH wild-type (majority of small cell GBMs that are lacking 1p/19q co-deletion and are having a high frequency of EGFR amplification); (ii) GBM, IDH mutated (predominantly secondary GBMs); and, (iii) anaplastic oligodendroglioma (1p/19q co-deleted and IDH mutated). It would, therefore, have been interesting to study the IDH status in the tumours of the present series.

EGFR amplification and TP53 mutation are mutually exclusive events in gliomas. But, p53 protein expression by immunohistochemistry, especially its focal staining, often does not correlate with TP53 gene mutation status.[8] This explains the lack of significant correlation between p53 immunopositivity and EGFR amplification in the present study.

EGFR amplification occurs in approximately 40% of primary GBMs, but rarely in secondary GBMs. Of the molecular subtypes, EGFR amplification is characteristic of the classical subtype which is associated with a more aggressive biological behaviour and a poor clinical outcome.[9] Approximately 20-50% of GBMs with EGFR amplification also harbour EGFRvIII which is potentially associated with a worse clinical outcome.[10] It would, therefore, have been interesting to assess the prognostic implication of EGFR amplification in this large cohort of GBMs.

The present elegant study thus adequately highlights the importance of EGFR amplification as a diagnostic marker of GBMs and supports the incorporation of this genetic marker using FISH technique as an integral part of the routine neuropathology practice, inspite of the cost implications.


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