Aberrant nuclear immunoreactivity for β-catenin and absent staining for CD34 were the most useful studies to diagnose fibromatosis, and one or both were performed in 21 (68%) cases.
Mutational analysis of exon 3 of the β-catenin gene (CTNNB1) revealed that mesenteric desmoids carried mutations significantly more often (51/56, 91.1%) than non-mesenteric tumours (20/28; 71.4%; P = 0.027). p.T41A occurred significantly more frequently in mesenteric fibromatoses (80.4%) than in abdominal wall and extra-abdominal fibromatoses (46.4%; P = 0.002).
Similar to adult sarcoma and fibromatosis, β-catenin was not expressed in the majority of childhood sarcomas, and its nuclear translocation was detected in paediatric fibromatosis; non-negligible levels of nuclear staining in other tumour types demonstrate Wnt pathway activation in mesenchymal neoplasms of childhood and adolescence.
Mutations in exon 3 of CTNNB1 were detected by direct DNA sequencing in nine (75.0%) cases: all were c.121G>A (p.T41A), which was much more frequent in breast fibromatoses than in other soft tissue lesions.
We searched for beta-catenin mutations in a European multicentre series of fibromatosis tumours to relate beta-catenin mutational status to disease outcome.
These findings indicate that alterations of the APC/beta-catenin pathway with resultant nuclear translocation of beta-catenin are important in the pathogenesis of both sporadic and FAP-associated breast fibromatosis.
In contrast to deep fibromatoses, superficial fibromatoses lack beta-catenin and APC gene mutations; the significance of focal nuclear beta-catenin accumulation is unclear.
These investigations suggest that, apart from their function in carcinogenesis and fibromatoses, APC and beta-catenin play a role in the pathogenesis of soft tissue tumors such as ASPS.
Fibromatosis in patients with familial adenomatous polyposis (FAP) harbours inactivating germline mutations in the desmoid region of the adenomatous polyposis coli (APC) gene on 5q21-q22.
These findings indicate that alterations of the APC/beta-catenin pathway with resultant nuclear translocation of beta-catenin are important in the pathogenesis of both sporadic and FAP-associated breast fibromatosis.
In contrast to deep fibromatoses, superficial fibromatoses lack beta-catenin and APC gene mutations; the significance of focal nuclear beta-catenin accumulation is unclear.
Changes of chromosome 5q, the region that includes the APC-gene, are known to be important in the pathogenesis of fibromatosis; however, little is known about the significance of APC and beta-catenin in other mesenchymal tumors.
This pilot project analyzed the tumor suppressor genes p53 and Rb in 13 cases of aggressive fibromatoses and six cases of palmar fibromatoses (Dupuytren contracture).