Publication: 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
Authors
Thoury, Anne ; Descatoire, Véronique ; Kotelevets, Larissa ; Kannengiesser, Caroline ; Bertrand, Guylène ; Theou-Anton, Nathalie ; Frey, Caroline ; Genestie, Catherine ; Raymond, Eric ; Chastre, Eric ; Lehy, Thérèse ; Walker, Francine
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Publisher
F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología
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DOI
https://doi.org/10.14670/HH-29.1455
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info:eu-repo/semantics/article
Description
Abstract
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, 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.
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