Identification of Familial Adenomatous Polyposis carriers among children with desmoid tumours

Anna A Kattentidt Mouravieva, Ina R R Geurts-Giele, Ronald R de Krijger, Max M van Noesel, Cees P van de Ven, Ans M W van den Ouweland, Joan N R Kromosoeto, Winand N M Dinjens, Hendrikus J Dubbink, Ron Smits, Anja Wagner

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

Samenvatting

OBJECTIVE: Desmoid tumours are rare mesenchymal tumours with unpredictable progression and high recurrence risk. They can occur sporadically or in association with Familial Adenomatous Polyposis (FAP), which is caused by germline APC mutations. The Wnt/β-catenin pathway has a central role in the pathogenesis of desmoid tumours. These tumours can occur due to either a somatic CTNNB1 or APC mutation but can also be the first manifestation of FAP. Because germline APC analysis is not routinely performed in children with desmoid tumours, the diagnosis FAP may escape detection. The aim of this study is to form guidelines for the identification of possible APC germline mutation carriers among children with desmoid tumours, based on CTNNB1 mutation analysis and immunohistochemical analysis (IHC) for β-catenin.

PATIENTS AND METHODS: We performed IHC of β-catenin and mutation analysis of CTNNB1 and APC in 18 paediatric desmoid tumours, diagnosed between 1990 and 2009 in the Erasmus MC, Rotterdam.

RESULTS: In 11 tumours, IHC showed an abnormal nuclear β-catenin accumulation. In this group a CTNNB1 mutation was detected in seven tumours. In two tumours with an abnormal nuclear β-catenin accumulation and no CTNNB1 mutation, an APC mutation was identified, which appeared to be a germline mutation.

CONCLUSIONS: Aberrant staining of β-catenin in paediatric desmoids helps to identify children at risk for FAP. We recommend to screen paediatric desmoid tumours for nuclear localisation of β-catenin and consequently for CTNNB1 mutations. For patients with nuclear β-catenin expression and no CTNNB1 mutations, APC mutation analysis should be offered after genetic counselling.

Originele taal-2Engels
Pagina's (van-tot)1867-74
Aantal pagina's8
TijdschriftEuropean Journal of Cancer
Volume48
Nummer van het tijdschrift12
DOI's
StatusGepubliceerd - feb. 2012
Extern gepubliceerdJa

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