β-Catenin in Soft tissue Sarcomas: Expression is Related to Proliferative Activity in High-Grade Sarcomas

Kühnen, C.; Herter, Peter; Müller, Oliver; Muehlberger, Thomas; Krause, Larissa; Homann, H.-H.; Steinau, Hans Ulrich; Müller, Klaus‐Michael

doi:10.1038/modpathol.3880181

Cited by 53 publications

(32 citation statements)

References 42 publications

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“…17 Another study investigated the immunostaining pattern of b-catenin in fibromatosis, but did not separate nuclear staining from cytoplasmic staining in their data. 13 Our results indicate that nuclear b-catenin staining is a sensitive marker for desmoid-type fibromatosis, and when high-level staining is seen, it is quite specific for this tumor type, although a few other tumor types may also show such staining. In particular, solitary fibrous tumors, which share some histologic features, also showed high-level staining.…”

Section: Discussionmentioning

confidence: 52%

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Nuclear beta-catenin in mesenchymal tumors

et al. 2005

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b-Catenin is a crucial part of the Wnt and E-cadherin signalling pathways, which are involved in tumorigenesis. Dysregulation of these pathways allow b-catenin to accumulate and translocate to the nucleus, where it may activate oncogenes. Such nuclear accumulation can be detected by immunohistochemistry, which may be useful in diagnosis. Although the role of b-catenin has been established in various types of carcinomas, relatively little is known about its status in mesenchymal tumors. A number of studies suggest that b-catenin dysregulation is important in desmoid-type fibromatosis, as well as in synovial sarcoma. We wished to determine whether nuclear b-catenin expression is specific to and sensitive for particular bone and soft-tissue tumors, including sporadic desmoid-type fibromatosis. We studied the nuclear expression of b-catenin using tissue microarrays in a comprehensive range of bone and soft-tissue tumor types. A total of 549 cases were included in our panel. Nuclear immunohistochemical staining was determined to be either high level (425% of cells), low level (0-25%) or none. High-level nuclear b-catenin staining was seen in a very limited subset of tumor types, including desmoid-type fibromatosis (71% of cases), solitary fibrous tumor (40%), endometrial stromal sarcoma (40%) and synovial sarcoma (28%). Although occasional cases of fibrosarcoma, clear cell sarcoma and carcinosarcoma had high-level staining, no high-level nuclear b-catenin expression was seen in any of 381 fibrohistocytic, muscular, adipocytic, chondroid or osseous tumor cases representing 42 diagnostic categories. All primary immunostain tissue microarray images are made publicly accessible in a searchable database. High-level nuclear b-catenin staining serves as a useful diagnostic tool, as it is specific to a small subset of mesenchymal tumors.

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Section: Discussionmentioning

confidence: 52%

“…11 Nuclear localization may also be common in synovial sarcomas 12 and high-grade sarcomas with high proliferative activity. 13 However, there is little known about b-catenin expression in other mesenchymal tumors.…”

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confidence: 99%

Nuclear beta-catenin in mesenchymal tumors

et al. 2005

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“…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.…”

Section: Discussionmentioning

confidence: 99%

Superficial Fibromatoses are Genetically Distinct from Deep Fibromatoses

et al. 2001

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“…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. 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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2008

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Cranial fasciitis, an unusual fibroproliferative lesion that occurs in the scalp of infants, is considered a posttraumatic reactive process similar to nodular fasciitis. Its pathobiology has not been investigated. Over the last 15 years, we diagnosed cranial fasciitis in six children; in one case, the lesion recurred after 4 years. This lesion and two others showed aberrant, diffuse nuclear reactivity for b-catenin. One of the lesions with aberrant nuclear b-catenin occurred in a child with a history of familial adenomatous polyposis (FAP) and a germline frameshift adenomatous polyposis coli (APC) mutation, c.878delG. The other APC allele in this tumor showed an acquired nonsense mutation, c.4132C-T. Both these mutations lead to translation of a truncated APC protein. The other two cases of cranial fasciitis with aberrant nuclear b-catenin occurred sporadically. One of these showed a point mutation, c.122C-T, in exon 3 of CTNNB1. This mutation causes replacement of threonine with isoleucine at codon 41, leading to loss of a phosphorylation site in the b-catenin protein. The third case with nuclear b-catenin staining was the single one that showed recurrence. This tumor did not show mutations in exon 3 of CTNNB1 or in exons 8/9/16 of APC. The results of this small study indicate a dysregulation of the Wnt/b-catenin pathway in a subset of cranial fasciitis, suggesting that this subset is pathobiologically related to desmoid fibromatoses rather than to nodular fasciitis. Occasional cases of cranial fasciitis may be associated with FAP and serve as an early indicator of this disease, information that would be important in the early diagnosis of FAP in patients without a family history of polyposis.

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β-Catenin in Soft tissue Sarcomas: Expression is Related to Proliferative Activity in High-Grade Sarcomas

Cited by 53 publications

References 42 publications

Nuclear beta-catenin in mesenchymal tumors

Nuclear beta-catenin in mesenchymal tumors

Superficial Fibromatoses are Genetically Distinct from Deep Fibromatoses

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

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