High frequency of beta-catenin heterozygous mutations in extra-abdominal fibromatosis: a potential molecular tool for disease management.
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 beta-catenin mutations in a European multicentre series of fibromatosis tumours to relate beta-catenin mutational status to disease outcome.


METHODS
Direct sequencing of exon 3 beta-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 beta-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 beta-catenin mutational status. With a median follow-up of 62 months, 51 patients relapsed. Five-year recurrence-free survival was significantly worse in beta-catenin-mutated tumours regardless of a specific genotype, compared with wild-type tumours (49 vs 75%, respectively, P=0.02).


CONCLUSIONS
A high frequency (87%) of beta-catenin mutation hallmarks extra-abdominal fibromatosis from a large multicentric retrospective study. Moreover, wild-type beta-catenin seems to be an interesting prognostic marker that might be useful in the therapeutic management of extra-abdominal fibromatosis.
Dômont
J
J
Sarcoma Committee, Institut Gustave Roussy, Villejuif, France.
Salas
S
S
Lacroix
L
L
Brouste
V
V
Saulnier
P
P
Terrier
P
P
Ranchère
D
D
Neuville
A
A
Leroux
A
A
Guillou
L
L
Sciot
R
R
Collin
F
F
Dufresne
A
A
Blay
J-Y
JY
Le Cesne
A
A
Coindre
J-M
JM
Bonvalot
S
S
Bénard
J
J
D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005350:Fibroma / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D008297:Male; D025202:Molecular Diagnostic Techniques; D020125:Mutation, Missense / Q000502:physiology; D017063:Outcome Assessment, Health Care; D011379:Prognosis; D012189:Retrospective Studies; D051176:beta Catenin / Q000235:genetics* / Q000502:physiology
D014408:Biomarkers, Tumor; D051176:beta Catenin