Prognostic significance of histologic grade and nuclear expression of β-catenin in synovial sarcoma

Hasegawa, Tadashi; Yokoyama, Ryohei; Matsuno, Yoshihiro; Shimoda, Tadakazu; Hirohashi, Setsuo

doi:10.1053/hupa.2001.22764

Cited by 69 publications

(58 citation statements)

References 25 publications

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“…In addition, many synovial sarcoma cases showed nuclear staining, which is similar to reported data where a cut-off of 450% staining was used on whole sections (25 of 44 cases, 57%). 12 A notable proportion of endometrial stromal sarcoma and carcinosarcoma (spindle cell carcinoma) cases also showed such staining, which may be relevant in particular differential diagnostic settings. One case of fibrosarcoma and one case of clear cell sarcoma did show high-level staining, but since our panel included only three cases of each tumor type, further studies are needed to investigate b-catenin in these two sarcomas.…”

Section: Discussionmentioning

confidence: 95%

“…There are no current data linking b-catenin to the pathogenesis 19 Furthermore, our data relating to synovial sarcoma is consistent with published reports, as APC mutations have been observed, 20 and b-catenin mutations and nuclear accumulation have been correlated with poor prognosis in this tumor type. 12,21 Tissue microarray technology allows high throughput immunohistochemical analysis of archival material, with parallel processing of specimens, and is increasingly being used in pathology investigations. Using duplicate cores helps reduce sampling errors, 22,23 but the extent of focal staining might still be underestimated using this technique.…”

Section: Discussionmentioning

confidence: 99%

“…One study has shown that nuclear expression of b-catenin may be used to distinguish mesenteric fibromatosis from gastrointestinal stromal tumors. 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%

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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: 95%

Section: Discussionmentioning

confidence: 99%

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Nuclear beta-catenin in mesenchymal tumors

et al. 2005

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“…On the other hand, membranous CD99 staining in synovial sarcoma may actually be helpful in differentiatiating monophasic or poorly differentiated synovial sarcoma from morphologically similar malignant peripheral nerve sheath tumor, since no malignant peripheral nerve sheath tumor stained with a membranous pattern in our study set. Other purportedly useful markers of synovial sarcoma, beta-catenin, MMP-2, and calponin, [16][17][18] were seemingly useless in our data set. For example, beta-catenin marked significant numbers of both malignant peripheral nerve sheath tumors and Ewing sarcomas and thus had low specificity.…”

Section: Discussionmentioning

confidence: 96%

“…10 A number of other antibodies have been touted as useful for these tumor types. For example, cytokeratin subsets, especially CK7 and 19, 3,9,14 bcl-2, 15 CD56, 9 calponin, 16 beta-catenin, 17 and matrix metalloproteinase-2 (MMP-2) 18 have been reported as potentially useful in synovial sarcoma; p75 nerve growth factor receptor (NGFR), 19 nestin, 20 CD57, 7,21,22 CD34, 22 PGP9.5, 23 and GFAP 21 in malignant peripheral nerve sheath tumor; Fli-1 in Ewing sarcoma; 6 and neuroectodermal markers such as chromoganin, synaptophysin, and PGP9.5 in primitive neuroectodermal tumor. [24][25][26][27] In order to further characterize the immunohistochemical profiles of synovial sarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma in a model that mimics small biopsy sampling, we evaluated a series of 73 tumors in tissue microarrays with a panel of 22 antibodies potentially useful in the differential diagnosis.…”

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Cluster analysis of immunohistochemical profiles in synovial sarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma

2006

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As a result of overlapping morphologic and immunohistochemical features, it can be difficult to distinguish synovial sarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma/primitive neuroectodermal tumor in core biopsies. To analyze and compare immunohistochemical profiles, we stained tissue microarrays of 23 synovial sarcomas, 23 malignant peripheral nerve sheath tumors, and 27 Ewing sarcomas with 22 antibodies potentially useful in the differential diagnosis, and analyzed the data with cluster analysis. Stain intensity was scored as none, weak, or strong. For CD99, tumors with membranous accentuation were independently categorized. Cluster analysis sorted five groups, with like tumors clustering together. Synovial sarcoma clustered into two groups: one cytokeratin and EMA positive (n ¼ 11), the other mostly cytokeratin negative, EMA positive, bcl-2 positive and mostly CD56 positive (n ¼ 9). Malignant peripheral nerve sheath tumor clustered into two groups: one S100 positive, with nestin and NGFR positivity in most (n ¼ 10), the other mostly S100 negative, and variably but mostly weakly positive for nestin and NGFR (n ¼ 11). Ewing sarcomas clustered into a single group driven by membranous CD99 staining. Thirteen cases failed to cluster (outliers), while three Ewing sarcomas clustered into groups of other tumor types. Paired antibodies for each tumor type determined by visual assessment of cluster analysis data and statistical calculations of specificity, sensitivity, and predictive values showed that EMA/CK7 for synovial sarcoma, nestin/S100 for malignant peripheral nerve sheath tumor, and membranous CD99/Fli-1 for Ewing sarcoma yielded high specificity and positive predictive values. Cluster analysis also highlighted aberrant staining reactions and diagnostic pitfalls in these tumors. Hierarchical cluster analysis is an effective method for analyzing high-volume immunohistochemical data.

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