EGFR Expression Pattern in Meningiomas
Angelique Guillaudeau, Karine Durand, Sandrine Robert, Francois Caire, Helene Rabinovitch-Chable, Francois Labrousse. Dupuytren University Hospital and Faculty of Medecine, Limoges, France
Background: In addition to EGFR variant 1 (v1) mRNA, which encodes the full-length receptor isoform a (EGFR or HER1), the EGFR gene is transcribed into 4 different alternatively spliced mRNAs variants referred to as variants 2 to 4 (EGFRv2 to -v4). These variants are shorter than EGFRv1 and encode truncated EGFR isoforms that lack the receptor's intracellular domain and, for two of them, a portion of the extracellular domain. The EGFRvIII mutant, encoding a constitutively active truncated receptor, is involved in gliomas oncogenesis. In meningiomas, EGFR expression pattern remains greatly unknown and studies mainly focused on EGFR isoform a and EGFRv1.
Design: In 69 meningiomas, histological tumor types and grade were determined according to the WHO classification. EGFRv1 to -v4 and EGFRvIII mRNAs were quantified by RT-PCR. Protein expression was investigated by immunohistochemistry using two antibodies: one directed against the extracellular domain recognized all the EGFR isoforms (Ext-Ab); a second one targeted against the intracellular domain only labeled EGFRv1 and -vIII (Int-Ab). Results were analyzed with respect to clinical data, histological typing, tumor grade, and patient outcome.
Results: There were 30 grade I, 32 grade II and 7 grade III. Meningiomas expressed EGFRv1 to -v4 mRNAs, but unlike in glioblastomas, EGFRvIII was not detected. EGFRv1, -v3 and -v4 mRNAs expression levels were significantly correlated. Tumor cells expressed EGFR protein and staining was stronger with Ext-Ab than with Int-Ab (p<0.0001). EGFRv1 to -v4 mRNAs expression levels as well as Ext-Ab or Int-Ab staining intensities were not related to tumor type and grade. Ki67 labeling index (LI) was higher in grade III vs. grade II and I meningiomas (p<0.005). Progression free survival was significantly improved in female patients, when tumor resection was evaluated as Simpson 1 or 2, in grade I vs. grade II and III meningiomas, in cases with a Ki67 LI lower than 10%, in tumors having intermediate or high Ext-Ab staining and when expression of all the EGFR variants (v1 to -v4) was high.
Conclusions: Our results suggest that all the EGFR variants and isoforms are expressed in meningiomas, except mutant vIII. In addition, high expression levels seem to be related to a better prognosis. This would suggest that the oncogenetic mechanisms involving the EGFR gene pathway are different in meningiomas and in glioblastomas.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 267, Tuesday Afternoon