Mutations in CTNNB1 but not AXIN2 in Aldosterone Producing Adenomas with Activated WNT/ BETA-catenin Signaling Pathway

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 17-28-Adrenal Tumors & Pheochromocytoma
Basic/Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-24
Tobias Åkerström*1, Rajani Maharjan1, Peter StÃ¥lberg2, Peyman Björklund2 and Per Hellman2
1Uppsala University, 2Uppsala University, Uppsala, Sweden
Mutations in CTNNB1 but not AXIN2 in Aldosterone Producing Adenomas with Activated WNT/ β-catenin Signaling Pathway

Tobias Åkerström1, Rajani Maharjan1, Peter Stålberg2, Per Hellman1 and Peyman Björklund1

1Experimental Surgery and 2Endocrine Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

 

Introduction: Activated WNT/ β-catenin signaling pathway is one of the most frequently found aberrancies in Aldosterone Producing Adenomas or APAs (2/3 of all tumors); however the underlying mechanisms are not identified. Mutations in CTNNB1 are associated with activated WNT signaling and are common in other adrenocortical tumors, but CTNNB1 mutation frequency in APAs is still unknown. AXIN2 is a negative regulator of WNT signaling pathway. Mutations in AXIN2 have been described in many tumors, amongst them adrenocortical tumors, however mutation status of AXIN2 in APAs have yet not been investigated.

   In this study we have screened a large cohort of APAs for mutations in CTNNB1 and AXIN2.

Materials and methods: 105 clinically and pathologically verified APAs from five different European centers were analyzed for mutations in selected coding exons of CTNNB1 and AXIN2, using automated Sanger sequencing. All tumors were previously screened for KCNJ5 mutation. Immunohistochemistry and western blot for β-catenin was conducted on selected samples.

Results: CTNNB1 mutations were found in 6 APAs (5.7%). Mutations in CTNNB1 were all previously described (S45P, S45F and T41A) and all mutated tumors had increased β-catenin expression shown by IHC and/or Western blot. IHC revealed accumulation of β-catenin in a majority of tumors without detectable CTNNB1 mutations. KCNJ5 and CTNNB1 mutations were mutually exclusive. No mutations were found in AXIN2.

Conclusion: The WNT signal pathway is activated in a majority of APAs but mutations in CTNNB1 are less frequent (5.7%). This activation is most likely not due to mutations in AXIN2. CTNNB1 and KCNJ5 mutations are mutually exclusive possibly representing two distinct pathways in APA formation.

Nothing to Disclose: T, RM, PS, PB, PH

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm