Titre
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.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Histology and Histopathology
Auteur(s)
Thoury, A.
Auteure/Auteur
Descatoire, V.
Auteure/Auteur
Kotelevets, L.
Auteure/Auteur
Kannengiesser, C.
Auteure/Auteur
Bertrand, G.
Auteure/Auteur
Theou-Anton, N.
Auteure/Auteur
Frey, C.
Auteure/Auteur
Genestie, C.
Auteure/Auteur
Raymond, E.
Auteure/Auteur
Chastre, E.
Auteure/Auteur
Lehy, T.
Auteure/Auteur
Walker, F.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1699-5848
Statut éditorial
Publié
Date de publication
2014
Volume
29
Numéro
11
Première page
1455
Dernière page/numéro d’article
1466
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Molecular 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, c-Met was higher (P⟨0.03) in group 2 than in group 1; d) In group 1, EGFR was correlated with c-Met, phospho-mTOR, phospho-RPS6 and the global activity of the phospho-AKT/phospho-mTOR/phospho-RPS6 pathway. In group 2, EGFR was correlated only with the phospho-AKT/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, anti-EGFR agents and rapamycin derivatives (anti-mTOR) for group 1 and an anti c-MET/ligand complex for group 2.
PID Serval
serval:BIB_BCAB1533B517
PMID
Date de création
2015-02-11T11:09:07.531Z
Date de création dans IRIS
2025-05-21T01:55:00Z