?-catenin nuclear expression correlates with cyclin D1 overexpression in sporadic desmoid tumours

Saito, Tsuyoshi; Oda, Yoshinao; Tanaka, Kazuhiro; Matsuda, Shuichi; Tamiya, Sadafumi; Iwamoto, Yukihide; Tsuneyoshi, Masazumi

doi:10.1002/path.942

Cited by 85 publications

(92 citation statements)

References 22 publications

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“…Cyclin D1 and fra-1 were upregulated in 50% of the desmoid samples. The results for cyclin D1 expression in desmoids are comparable to those found by Saito et al (2001). No differential expression was observed for cjun, c-myc, and PPAR delta.…”

Section: Discussionsupporting

confidence: 82%

Identification of IGFBP-6 as a significantly downregulated gene by β-catenin in desmoid tumors

et al. 2004

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Section: Discussionsupporting

confidence: 82%

Identification of IGFBP-6 as a significantly downregulated gene by β-catenin in desmoid tumors

et al. 2004

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“…21 It has also been clarified that 23 thyroid papillary carcinoma, 24 and desmoid tumor. 6 Our results raise the possibility that cyclin D1 may be upregulated through an activated Wnt/b-catenin pathway in undifferentiated endometrial sarcoma with nuclear uniformity. We consider that further studies to support this speculation would be of value because the Wnt signaling pathway and cyclin D1 could potentially be a future target of anticancer drugs.…”

Section: Discussionmentioning

confidence: 67%

“…4 As for cyclin D1, staining of more than 5% of the tumor nuclei was needed for a case to be scored positive. 6 The MIB-1 labeling index, which refers to a percentage of positive tumor cells, was determined by counting at least 500 tumor cells.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…4 Some kinds of mesenchymal tumors such as desmoid tumor and synovial sarcoma also frequently show nuclear accumulation of b-catenin. 5,6 Regarding endometrial stromal sarcoma, Ng et al 4 have reported that high-level nuclear b-catenin staining is seen in 40% of endometrial stromal sarcoma. We have also reported that 47% of lowgrade endometrial stromal sarcoma and 85% of undifferentiated endometrial sarcoma featuring uniform nuclei show nuclear b-catenin expression.…”

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confidence: 99%

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Coincident expression of β-catenin and cyclin D1 in endometrial stromal tumors and related high-grade sarcomas

et al. 2010

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Aberrant activation of the Wnt signaling pathway has been implicated in tumorigenesis of a wide range of tumors, including colorectal cancer. Regarding endometrial stromal tumors and related high-grade sarcomas, there have been some reports regarding nuclear accumulation of b-catenin. To clarify the function of the aberrant Wnt signaling pathway in these tumors, we searched for mutations of the CTNNB1 (b-catenin) gene and APC gene by PCR direct sequencing and analyzed the methylation status of SFRP genes. We also examined overexpression of cyclin D1 and MMP-7, which are direct target genes of b-catenin. Eight endometrial stromal nodules, 16 low-grade endometrial stromal sarcomas, and 13 undifferentiated endometrial sarcomas were examined. PCR and direct sequencing revealed no mutation of the b-catenin gene or the APC gene. Concerning the promoter methylation status of SFRP genes, methylation-specific PCR revealed no significant difference between the group with nuclear b-catenin expression and that without nuclear b-catenin expression. Immunohistochemistry revealed overexpression of cyclin D1 in 2 out of 8 endometrial stromal nodules, 1 out of 17 low-grade endometrial stromal sarcomas, and 6 out of 13 undifferentiated endometrial sarcomas, and these 6 undifferentiated endometrial sarcomas simultaneously expressed nuclear b-catenin. Interestingly, all six undifferentiated endometrial sarcoma cases with cyclin D1 overexpression histologically featured rather uniform nuclei. In contrast, the six cases of undifferentiated endometrial sarcoma with highly pleomorphic nuclei were all negative for cyclin D1. In conclusion, among endometrial stromal tumors and related sarcomas, undifferentiated endometrial sarcomas featuring uniform nuclei were characterized by frequent coincident expression of b-catenin and cyclin D1. This finding raises the possibility that cyclin D1 is upregulated by b-catenin in these high-grade sarcomas previously called high-grade endometrial stromal sarcoma.

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“…It is known that dysregulation of b-catenin is important in the development of both an inherited predisposition to fibromatosis, as part of the Gardner syndrome (with familial adenomatous polyposis), and in sporadic desmoid-type fibromatosis. [4][5][6][7][8] Dysregulation of this pathway has also been demonstrated in synovial sarcomas, osteosarcomas, 9 liposarcomas and malignant fibrous histiocytomas. 10 To demonstrate such dysregulation of this pathway, immunohistochemistry has been used to show abnormal nuclear accumulation of b-catenin.…”

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confidence: 99%

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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?-catenin nuclear expression correlates with cyclin D1 overexpression in sporadic desmoid tumours

Cited by 85 publications

References 22 publications

Identification of IGFBP-6 as a significantly downregulated gene by β-catenin in desmoid tumors

Identification of IGFBP-6 as a significantly downregulated gene by β-catenin in desmoid tumors

Coincident expression of β-catenin and cyclin D1 in endometrial stromal tumors and related high-grade sarcomas

Nuclear beta-catenin in mesenchymal tumors

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