EGFR soluble isoforms and their transcripts are expressed in meningiomas.

The EGFR (epidermal growth factor receptor) is involved in the oncogenesis of many tumors. In addition to the full-length EGFR (isoform a), normal and tumor cells produce soluble EGFR isoforms (sEGFR) that lack the intracellular domain. sEGFR isoforms b, c and d are encoded by EGFR variants 2 (v2),...

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Autores principales:	Angélique Guillaudeau, Karine Durand, Barbara Bessette, Alain Chaunavel, Isabelle Pommepuy, Fabrice Projetti, Sandrine Robert, François Caire, Hélène Rabinovitch-Chable, François Labrousse
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/27b31970fd2649008dc0c26cd0566914
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spelling	oai:doaj.org-article:27b31970fd2649008dc0c26cd05669142021-11-18T07:18:11ZEGFR soluble isoforms and their transcripts are expressed in meningiomas.1932-620310.1371/journal.pone.0037204https://doaj.org/article/27b31970fd2649008dc0c26cd05669142012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22623992/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The EGFR (epidermal growth factor receptor) is involved in the oncogenesis of many tumors. In addition to the full-length EGFR (isoform a), normal and tumor cells produce soluble EGFR isoforms (sEGFR) that lack the intracellular domain. sEGFR isoforms b, c and d are encoded by EGFR variants 2 (v2), 3 (v3) and 4 (v4) mRNA resulting from gene alternative splicing. Accordingly, the results of EGFR protein expression analysis depend on the domain targeted by the antibodies. In meningiomas, EGFR expression investigations mainly focused on EGFR isoform a. sEGFR and EGFRvIII mutant, that encodes a constitutively active truncated receptor, have not been studied. In a 69 meningiomas series, protein expression was analyzed by immunohistochemistry using extracellular domain targeted antibody (ECD-Ab) and intracellular domain targeted antibody (ICD-Ab). EGFRv1 to v4 and EGFRvIII mRNAs were quantified by RT-PCR and EGFR amplification revealed by MLPA. Results were analyzed with respect to clinical data, tumor resection (Simpson grade), histological type, tumor grade, and patient outcome.Immunochemical staining was stronger with ECD-Ab than with ICD-Ab. Meningiomas expressed EGFRv1 to -v4 mRNAs but not EGFRvIII mutant. Intermediate or high ECD-Ab staining and high EGFRv1 to v4 mRNA levels were associated to a better progression free survival (PFS). PFS was also improved in women, when tumor resection was evaluated as Simpson 1 or 2, in grade I vs. grade II and III meningiomas and when Ki67 labeling index was lower than 10%. Our results suggest that, EGFR protein isoforms without ICD and their corresponding mRNA variants are expressed in meningiomas in addition to the whole isoform a. EGFRvIII was not expressed. High expression levels seem to be related to a better prognosis. These results indicate that the oncogenetic mechanisms involving the EGFR pathway in meningiomas could be different from other tumor types.Angélique GuillaudeauKarine DurandBarbara BessetteAlain ChaunavelIsabelle PommepuyFabrice ProjettiSandrine RobertFrançois CaireHélène Rabinovitch-ChableFrançois LabroussePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37204 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Angélique Guillaudeau Karine Durand Barbara Bessette Alain Chaunavel Isabelle Pommepuy Fabrice Projetti Sandrine Robert François Caire Hélène Rabinovitch-Chable François Labrousse EGFR soluble isoforms and their transcripts are expressed in meningiomas.
description	The EGFR (epidermal growth factor receptor) is involved in the oncogenesis of many tumors. In addition to the full-length EGFR (isoform a), normal and tumor cells produce soluble EGFR isoforms (sEGFR) that lack the intracellular domain. sEGFR isoforms b, c and d are encoded by EGFR variants 2 (v2), 3 (v3) and 4 (v4) mRNA resulting from gene alternative splicing. Accordingly, the results of EGFR protein expression analysis depend on the domain targeted by the antibodies. In meningiomas, EGFR expression investigations mainly focused on EGFR isoform a. sEGFR and EGFRvIII mutant, that encodes a constitutively active truncated receptor, have not been studied. In a 69 meningiomas series, protein expression was analyzed by immunohistochemistry using extracellular domain targeted antibody (ECD-Ab) and intracellular domain targeted antibody (ICD-Ab). EGFRv1 to v4 and EGFRvIII mRNAs were quantified by RT-PCR and EGFR amplification revealed by MLPA. Results were analyzed with respect to clinical data, tumor resection (Simpson grade), histological type, tumor grade, and patient outcome.Immunochemical staining was stronger with ECD-Ab than with ICD-Ab. Meningiomas expressed EGFRv1 to -v4 mRNAs but not EGFRvIII mutant. Intermediate or high ECD-Ab staining and high EGFRv1 to v4 mRNA levels were associated to a better progression free survival (PFS). PFS was also improved in women, when tumor resection was evaluated as Simpson 1 or 2, in grade I vs. grade II and III meningiomas and when Ki67 labeling index was lower than 10%. Our results suggest that, EGFR protein isoforms without ICD and their corresponding mRNA variants are expressed in meningiomas in addition to the whole isoform a. EGFRvIII was not expressed. High expression levels seem to be related to a better prognosis. These results indicate that the oncogenetic mechanisms involving the EGFR pathway in meningiomas could be different from other tumor types.
format	article
author	Angélique Guillaudeau Karine Durand Barbara Bessette Alain Chaunavel Isabelle Pommepuy Fabrice Projetti Sandrine Robert François Caire Hélène Rabinovitch-Chable François Labrousse
author_facet	Angélique Guillaudeau Karine Durand Barbara Bessette Alain Chaunavel Isabelle Pommepuy Fabrice Projetti Sandrine Robert François Caire Hélène Rabinovitch-Chable François Labrousse
author_sort	Angélique Guillaudeau
title	EGFR soluble isoforms and their transcripts are expressed in meningiomas.
title_short	EGFR soluble isoforms and their transcripts are expressed in meningiomas.
title_full	EGFR soluble isoforms and their transcripts are expressed in meningiomas.
title_fullStr	EGFR soluble isoforms and their transcripts are expressed in meningiomas.
title_full_unstemmed	EGFR soluble isoforms and their transcripts are expressed in meningiomas.
title_sort	egfr soluble isoforms and their transcripts are expressed in meningiomas.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/27b31970fd2649008dc0c26cd0566914
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EGFR soluble isoforms and their transcripts are expressed in meningiomas.

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