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, 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.
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Authors | Anne Thoury, Véronique Descatoire, Larissa Kotelevets, Caroline Kannengiesser, Guylène Bertrand, Nathalie Theou-Anton, Caroline Frey, Catherine Genestie, Eric Raymond, Eric Chastre, Thérèse Lehy, Francine Walker |
Journal | Histology and histopathology
(Histol Histopathol)
Vol. 29
Issue 11
Pg. 1455-66
(Nov 2014)
ISSN: 1699-5848 [Electronic] Spain |
PMID | 24811063
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Ki-67 Antigen
- Ligands
- MTOR protein, human
- Class I Phosphatidylinositol 3-Kinases
- PIK3CA protein, human
- EGFR protein, human
- ErbB Receptors
- Proto-Oncogene Proteins c-met
- TOR Serine-Threonine Kinases
- PTEN Phosphohydrolase
- PTEN protein, human
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Carcinoma
(genetics, metabolism)
- Class I Phosphatidylinositol 3-Kinases
- DNA Mutational Analysis
- Endometrial Neoplasms
(genetics, metabolism)
- ErbB Receptors
(genetics)
- Female
- Gene Expression Profiling
- Gene Expression Regulation, Neoplastic
- Genes, ras
- Humans
- Immunohistochemistry
- Ki-67 Antigen
(metabolism)
- Ligands
- Microsatellite Instability
- Microsatellite Repeats
(genetics)
- Middle Aged
- Mutation
- PTEN Phosphohydrolase
(genetics)
- Phosphatidylinositol 3-Kinases
(genetics)
- Proto-Oncogene Proteins c-met
(genetics)
- Retrospective Studies
- TOR Serine-Threonine Kinases
(genetics)
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