Predominance of beta-catenin mutations and beta-catenin dysregulation in sporadic aggressive fibromatosis (desmoid tumor)

Superficial Fibromatoses are Genetically Distinct from Deep Fibromatoses

“…The ␤-catenin and APC genes are closely interrelated and play a significant role in epithelial neoplasms, best studied in colon cancer (18, 26 -39), but also in deep fibromatoses (19,40) and sarcomas (41). ␤-catenin is an intracellular protein that is regulated by the APC protein.…”

“…As the various FAP-associated tumors have been studied, somatic alterations of the APC/␤-catenin pathway have been initially detected in familial examples and then subsequently demonstrated in the sporadic counterparts. The first studied tumors were gastrointestinal adenomas (30,38,39,58), followed by desmoid tumors (16,18,19), medulloblastomas (59), childhood hepatoblastomas (60,61), and gastric fundic gland polyps (24,25). More recently, the same story has unfolded in juvenile nasopharyngeal angiofibromas (22,62), which occur more frequently in FAP patients than in controls.…”

“…This observation has led to the study of APC mutations in sporadic desmoid tumors. Because one function of the APC gene involves regulation of the cellular level of ␤-catenin, the interaction between these two molecules has been explored in tandem, and although sporadic desmoid tumors may have APC mutations (16,17), they are more likely to have ␤-catenin mutations (18,19). It appears that the majority of desmoid tumors, both familial and sporadic, have mutations of one of these two genes.…”

A subset of cranial fasciitis is associated with dysregulation of the Wnt/β-catenin pathway

“…15,16 In contrast to the purely membranous localization in normal epithelial cells, b-catenin staining in mesenchymal cells is limited to the cytoplasm and/or the cell membranes. 17 b-catenin may be involved in normal wound healing and abnormal proliferations of fibroblasts. 18 Among mesenchymal tumors, aberrant localization of b-catenin has been described in solitary fibrous tumors, osteosarcomas, malignant phyllodes tumors, liposarcomas, malignant fibrous histiocytomas, synovial sarcomas, malignant peripheral nerve sheath tumors and myxofibrosarcomas, [19][20][21][22][23][24] but the dysregulation and nuclear localization of b-catenin is most strongly associated with desmoid fibromatoses and Gardner fibromas, both sporadic and those associated with FAP and its variant syndromes.…”

“…18 Among mesenchymal tumors, aberrant localization of b-catenin has been described in solitary fibrous tumors, osteosarcomas, malignant phyllodes tumors, liposarcomas, malignant fibrous histiocytomas, synovial sarcomas, malignant peripheral nerve sheath tumors and myxofibrosarcomas, [19][20][21][22][23][24] but the dysregulation and nuclear localization of b-catenin is most strongly associated with desmoid fibromatoses and Gardner fibromas, both sporadic and those associated with FAP and its variant syndromes. 17,[25][26][27][28][29] By immunohistochemistry, b-catenin is seen in the cytoplasm of the lesional cells of nodular fasciitis, with no accumulation in the nucleus. 30,31 Similar to the previous results, all of our nine cases of nodular fasciitis showed only cytoplasmic staining for b-catenin.…”