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https://doi.org/10.14670/HH-29.1455
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Título: | 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 |
Fecha de publicación: | 2014 |
Editorial: | F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología |
Cita bibliográfica: | Histology and Histopathology, Vol. 29, n.º 11 (2014) |
ISSN: | 0213-3911 1699-5848 |
Materias relacionadas: | CDU::5 - Ciencias puras y naturales::57 - Biología::576 - Biología celular y subcelular. Citología |
Palabras clave: | EGFR c-Met PTEN mTOR pathway |
Resumen: | 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. |
Autor/es principal/es: | 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 |
URI: | http://hdl.handle.net/10201/77384 |
DOI: | https://doi.org/10.14670/HH-29.1455 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 12 |
Derechos: | info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 International |
Aparece en las colecciones: | Vol.29, nº11 (2014) |
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Thoury-29-1455-1466-2014.pdf | 7,45 MB | Adobe PDF | Visualizar/Abrir |
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