Epidermal growth factor receptor, phosphatidylinositol-3-kinase catalytic subunit/PTEN, and KRAS/NRAS/BRAF in primary resected esophageal adenocarcinomas: loss of PTEN is associated with worse clinical outcome.

Détails

ID Serval
serval:BIB_CBEF216CDFAA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Epidermal growth factor receptor, phosphatidylinositol-3-kinase catalytic subunit/PTEN, and KRAS/NRAS/BRAF in primary resected esophageal adenocarcinomas: loss of PTEN is associated with worse clinical outcome.
Périodique
Human pathology
Auteur⸱e⸱s
Bettstetter M. (co-premier), Berezowska S. (co-premier), Keller G., Walch A., Feuchtinger A., Slotta-Huspenina J., Feith M., Drecoll E., Höfler H., Langer R.
ISSN
1532-8392 (Electronic)
ISSN-L
0046-8177
Statut éditorial
Publié
Date de publication
05/2013
Peer-reviewed
Oui
Volume
44
Numéro
5
Pages
829-836
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Alterations of the epidermal growth factor receptor (EGFR) can be observed in a significant subset of esophageal adenocarcinomas (EACs), and targeted therapy against EGFR may become an interesting approach for the treatment of these tumors. Mutations of KRAS, NRAS, BRAF, and phosphatidylinositol-3-kinase catalytic subunit (PIK3CA) and deregulation of PTEN expression influence the responsiveness against anti-EGFR therapy in colorectal carcinomas. We investigated the prevalence of these events in a collection of 117 primary resected EACs, correlated the findings with EGFR expression and amplification, and determined their clinicopathologic impact. KRAS mutations were detected in 4 (3%) of 117 tumors (3× G12D and 1 G12V mutation). One tumor had a PIK3CA E545K mutation. Neither NRAS nor BRAF mutations were detected. Sixteen (14%) of 117 cases were negative for PTEN expression, determined by immunohistochemistry. Loss of PTEN was observed predominantly in advanced tumor stages (P = .004). There was no association between PTEN and EGFR status. Loss of PTEN was associated with shorter overall and disease-free survival (P < .001 each) and also an independent prognostic factor in multivariate analysis (P = .015). EGFR status had no prognostic impact in this case collection. In summary, loss of PTEN can be detected in a significant subset of EAC and is associated with an aggressive phenotype. Therefore, PTEN may be useful as a prognostic biomarker. In contrast, mutations of RAS/RAF/PIK3CA appear only very rarely, if at all, in EAC. A possible predictive role of PTEN in anti-EGFR treatment warrants further investigations, whereas determination of RAS/RAF/PIK3CA mutations may only have a minor impact in this context.
Mots-clé
Adenocarcinoma/genetics, Adenocarcinoma/mortality, Adenocarcinoma/pathology, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor/metabolism, Catalytic Domain, Class I Phosphatidylinositol 3-Kinases, Class Ia Phosphatidylinositol 3-Kinase/genetics, Disease-Free Survival, ErbB Receptors/genetics, Esophageal Neoplasms/genetics, Esophageal Neoplasms/mortality, Esophageal Neoplasms/pathology, Female, GTP Phosphohydrolases/genetics, Humans, Male, Membrane Proteins/genetics, Middle Aged, PTEN Phosphohydrolase/genetics, Phosphatidylinositol 3-Kinases/genetics, Prognosis, Proto-Oncogene Proteins/genetics, Proto-Oncogene Proteins B-raf/genetics, Proto-Oncogene Proteins p21(ras), ras Proteins/genetics
Pubmed
Web of science
Création de la notice
29/06/2020 11:18
Dernière modification de la notice
30/06/2020 5:26
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