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Evidence for different expression profiles for c-Met, EGFR, PTEN and the mTOR pathway in low and high grade endometrial carcinomas in a cohort of consecutive women. Occurrence of PIK3CA and K-Ras mutations and microsatellite instability

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dc.contributor.authorThoury, Anne
dc.contributor.authorDescatoire, Véronique
dc.contributor.authorKotelevets, Larissa
dc.contributor.authorKannengiesser, Caroline
dc.contributor.authorBertrand, Guylène
dc.contributor.authorTheou-Anton, Nathalie
dc.contributor.authorFrey, Caroline
dc.contributor.authorGenestie, Catherine
dc.contributor.authorRaymond, Eric
dc.contributor.authorChastre, Eric
dc.contributor.authorLehy, Thérèse
dc.contributor.authorWalker, Francine
dc.date.accessioned2019-12-09T16:46:52Z
dc.date.available2019-12-09T16:46:52Z
dc.date.issued2014
dc.description.abstractMolecular and genetic investigations in endometrial carcinogenesis may have prognostic and therapeutic implications. We studied the expression of EGFR, c-Met, PTEN and the mTOR signalling pathway (phospho-AKT/phospho-mTOR/phospho-RPS6) in 69 consecutive tumours and 16 tissue microarrays. We also analysed PIK3CA, K-Ras mutations and microsatellite instability (MSI). We distinguished two groups: group 1 (grade 1 and 2 endometrioid cancers) and group 2 (grade 3 endometrioid and type II clear and serous cell cancers). We hypothesised that these histological groups might have different features. We found that a) survival was higher in group 1 with less aggressive tumours (P<0.03); b) EGFR (P=0.01), PTEN and the AKT/mTOR/RPS6 signalling pathway were increased in group 1 versus group 2 (P=0.05 for phospho-mTOR); c) conversely, cMet was higher (P<0.03) in group 2 than in group 1; d) In group 1, EGFR was correlated with c-Met, phosphomTOR, phospho-RPS6 and the global activity of the phospho-AKT/phospho-mTOR/phospho-RPS6 pathway. In group 2, EGFR was correlated only with the phosphoAKT/phospho-mTOR/phospho-RPS6 pathway, whereas c-Met was correlated with PTEN; e) survival was higher for tumours with more than 50% PTEN-positive cells; f) K-RAS and PIK3CA mutations occurred in 10-12% of the available tumours and MSI in 40.4%, with a loss of MLH1 and PMS2 expression. Our results for endometrial cancers provide the first evidence for a difference in status between groups 1 and 2. The patients may benefit from different targeted treatments, antiEGFR agents and rapamycin derivatives (anti-mTOR) for group 1 and an anti c-MET/ligand complex for group 2.es
dc.formatapplication/pdfes
dc.format.extent12es
dc.identifier.doihttps://doi.org/10.14670/HH-29.1455
dc.identifier.eisbnHistology and Histopathology, Vol. 29, n.º 11 (2014)es
dc.identifier.issn0213-3911
dc.identifier.issn1699-5848
dc.identifier.urihttp://hdl.handle.net/10201/77384
dc.languageenges
dc.publisherF. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histologíaes
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectEGFRes
dc.subjectc-Metes
dc.subjectPTENes
dc.subjectmTOR pathwayes
dc.subject.otherCDU::5 - Ciencias puras y naturales::57 - Biología::576 - Biología celular y subcelular. Citologíaes
dc.titleEvidence for different expression profiles for c-Met, EGFR, PTEN and the mTOR pathway in low and high grade endometrial carcinomas in a cohort of consecutive women. Occurrence of PIK3CA and K-Ras mutations and microsatellite instabilityes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.29, nº11 (2014)