High frequency of Β-catenin heterozygous mutations in extra-abdominal fibromatosis: A potential molecular tool for disease management

J. Dômont, S. Salas, L. Lacroix, V. Brouste, P. Saulnier, P. Terrier, D. Ranchère, A. Neuville, A. Leroux, L. Guillou, R. Sciot, F. Collin, A. Dufresne, J. Y. Blay, A. Le Cesne, J. M. Coindre, S. Bonvalot, J. Benard

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    Abstract

    Background: Fibromatosis comprises distinct clinical entities, including sporadic extra-abdominal fibromatosis, which have a high tendency for recurrence, even after adequate resection. There are no known molecular biomarkers of local recurrence. We searched for Β-catenin mutations in a European multicentre series of fibromatosis tumours to relate Β-catenin mutational status to disease outcome. Methods: Direct sequencing of exon 3 Β-catenin gene was performed for 155 frozen fibromatosis tissues from all topographies. Correlation of outcome with mutation rate and type was performed on the extra-abdominal fibromatosis group (101 patients).Results: Mutations of Β-catenin were detected in 83% of all cases. Among 101 extra-abdominal fibromatosis, similar mutation rates (87%) were observed, namely T41A (39.5%), S45P (9%), S45F (36.5%), and deletion (2%). None of the clinico-pathological parameters were found to be significantly associated with Β-catenin mutational status. With a median follow-up of 62 months, 51 patients relapsed. Five-year recurrence-free survival was significantly worse in Β-catenin-mutated tumours regardless of a specific genotype, compared with wild-type tumours (49 vs 75%, respectively, P=0.02).Conclusion: A high frequency (87%) of Β-catenin mutation hallmarks extra-abdominal fibromatosis from a large multicentric retrospective study. Moreover, wild-type Β-catenin seems to be an interesting prognostic marker that might be useful in the therapeutic management of extra-abdominal fibromatosis.

    Original languageEnglish
    Pages (from-to)1032-1036
    Number of pages5
    JournalBritish Journal of Cancer
    Volume102
    Issue number6
    DOIs
    Publication statusPublished - 1 Mar 2010

    Keywords

    • Fibromatosis
    • Prognostic factor
    • β-catenin mutation

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