Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2012) 29 P40

ICEECE2012 Poster Presentations Adrenal cortex (113 abstracts)

The Wnt/Beta-catenin and Ras/Raf/MEK/ERK signaling pathways alterations in adrenocortical tumors

B. Rubin , R. Pezzani , S. Barollo , B. Mariniello , M. Salvà , M. Iacobone , A. Fassina & F. Mantero


University of Padua, Padua, Italy.


Adrenocortical tumors (ACT) include benign and malignant tumors. Adrenocortical carcinomas (ACC) are highly malignant neoplasms with a poor prognosis, but their genetic alterations to date identified are limited. Laboratory studies on ACT have revealed a wide variety of signaling pathways involved in these tumors, among these Wnt/β-catenin signaling pathway and Ras/Raf/MEK/ERK pathway resulted often disregulated. Another important factor in many signaling pathways is the epidermal growth factor receptor (EGFR), responsible for proliferation and overexpressed in many adrenocortical tumors.

The objective of our study was to evaluate genetic alterations in key components of Wnt/β-catenin and Ras/Raf/MEK/ERK signaling pathways in order to better understand the pathogenesis of sporadic adrenocortical tumors and provide light onto new possible prognostic factors.

We performed high resolution melting (HRM) analysis for evaluating the presence of activating mutations in EGFR (exons 18, 19, 20, 21), BRAF (exons 11 and 15), H-RAS (exons 1 and 2), N-RAS (exons 1 and 2), K-RAS (exons 1 and 2), CTNNB1 (exon 3), AXIN2 (exon 7). We analyzed a series of 92 sporadic samples: 21 ACC, 38 aldosterone producing adenomas (APA), 29 cortisol producing adenomas (CPA) and 4 normal adrenocortical tissues. Only samples resulted with altered melting curves were direct sequencing.

We found 2 different BRAF mutations in 2 ACC, 4 H-RAS silent mutations in 1 APA, 1 CPA and in 2 ACC, 16 CTNNB1 alterations in 5 APA, 6 CPA and 5 ACC. No alteration in EGFR, N-RAS, K-RAS.

These results suggest that abnormalities in Ras/Raf/MEK/ERK pathway do not represent a frequent pathogenetic mechanism of adrenocortical tumorigenesis, while alterations in Wnt/β-catenin pathway seem to be a more common event. Nevertheless this study identified diverse genetic alterations, whose role in adrenocortical tumors should be further investigated.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.

Volume 29

15th International & 14th European Congress of Endocrinology

European Society of Endocrinology 

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