ECE2017 Guided Posters Adrenal 3 (12 abstracts)
Epithelial to mesenchymal transition in adrenocortical tumours: focus on FGF-FGFR pathway and c-MET
Iuliu Sbiera 1 , Barbara Altieri 1, , Annette Feuchtinger 3 , Kerstin Höfner 1 , Axel Walch 3 , Martin Fassnacht 1, , Cristina L Ronchi 1 , Matthias Kroiss 1, & Silviu Sbiera 1,
1Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Wuerzburg, Germany; 2Division of Endocrinology and Metabolic Diseases, Catholic University of the Sacred Heart, Rome, Italy; 3Research Unit Analytical Pathology, Helmholtz Zentrum München, Oberschleissheim, Germany; 4Comprehenssive Cancer Center Mainfranken, University of Würzburg, Wuerzburg, Germany; 5Clinical Chemistry and Laboratory Medicine, University Hospital, University of Würzburg, Wuerzburg, Germany.
Ad Adrenocortical carcinoma (ACC) is an aggressive tumour and treatment remains unsatisfactory in advanced disease. Activation of epithelial to mesenchymal transition (EMT) is considered causative for metastatic spread in a variety of human cancers. Accordingly, new drugs were developed specifically targeting EMT with a focus on hepatocyte growth factor (HGF)/HGF receptor (c-MET) and fibroblast growth factor (FGF)/FGF receptor (FGFR) signalling.
We here asked whether EMT is relevant to ACC progression to evaluate the therapeutic potential of small molecule drugs targeting EMT.
Expression of FGFR family members and c-MET was analysed in 20 normal adrenal glands (NAG), 23 adrenocortical adenomas(ACA) and 27 ACC at mRNA and protein level. Expression of FGFR1-4 was quantified in FFPE tumour tissue using RNAscope mRNA in situ hybridization technique. c-MET mRNA was quantified by qRT-PCR. In a subset of 40 samples we quantified expression of 92 different genes involved in FGF-FGFR pathway signalling.
FGFR2 mRNA was lower in ACC compared to ACA (3.1±2.1 vs 6.5±2.3 mRNA copies/cell, P=0.0005) whereas FGFR1 (7.5±5.3 vs 4.5±2.9, P=0.09) and FGFR4 (5.1±2.3 vs 2.6±1.3, P=0.002) were higher in ACC. FGFR4 expression was higher in advanced vs localized ACC (6.2±1.6 vs 3.9±2.7, P=0.03). Pan-FGF-FGFR pathway qRT-PCR confirmed differential FGFR expression and revealed decreased expression of FGF7, FGF17 and mitogen associated protein kinases in tumours compared with NAG. In advanced ACC protein kinase c PRKCA was decreased but PRKCQ increased.
c-MET mRNA expression was significantly higher in ACC compared to ACA and NAG (0.03±0.05 vs 0.01±0.03 and 0.01±0.02, respectively, P=0.02). Considering median expression as a cut-off, high c-MET expression in ACC was associated with decreased overall survival (HR=8.8, P=0.02).
In conclusion, EMT appears to be relevant for adrenocortical tumourigenesis and progression. PRKCQ may be involved in EMT signalling in advanced ACC. EMT-related kinases such as c-MET and FGFR4 may be suitable treatment targets in advanced ACC.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more