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在梭形和多形性肉瘤中,细胞核β-连环蛋白与细胞周期蛋白D1表达相关,但在滑膜肉瘤中并非如此。

Nuclear beta-catenin correlates with cyclin D1 expression in spindle and pleomorphic sarcomas but not in synovial sarcoma.

作者信息

Saito Tsuyoshi, Oda Yoshinao, Yamamoto Hidetaka, Kawaguchi Ken-Ichi, Tanaka Kazuhiro, Matsuda Shuichi, Iwamoto Yukihide, Tsuneyoshi Masazumi

机构信息

Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

出版信息

Hum Pathol. 2006 Jun;37(6):689-97. doi: 10.1016/j.humpath.2006.01.017.

Abstract

Nuclear beta-catenin staining in soft tissue sarcomas (STSs) has been shown to correlate with tumor progression as assessed by proliferative activity or poor prognosis. Frequent activation of Wnt signaling pathway has been also shown in synovial sarcoma (SS), suggesting a specific role of this pathway in SS. We examined roles of nuclear beta-catenin staining within soft tissue sarcomas. Immunohistochemical detection of nuclear beta-catenin accumulation correlated with cyclin D1 overexpression in spindle cell and pleomorphic sarcomas (P = .037), and the expression of these proteins evenly distributed throughout each section. In some cases, strong beta-catenin nuclear staining was observed in highly pleomorphic and mitotic cells. Furthermore, tumors with nuclear beta-catenin accumulation showed statistically significant increasing cyclin D1 mRNA expression level compared with those without (P = .023). Cyclin D1 mRNA expression levels were statistically higher in tumors with cyclin D1 overexpression than in tumors without (P = .037), suggesting that cyclin D1 overexpression is due to transcriptional activation. However, these correlations could not be detected in SS. In biphasic SS, beta-catenin nuclear staining was observed in spindle cells, whereas cyclin D1 nuclear staining was seen in glandular areas where beta-catenin kept membranous expression. Mutations in exon 3 of the beta-catenin gene and in the mutation cluster region of adenomatous polyposis coli gene were absent in this series of cases. Thus, cyclin D1 could be considered as one of the targets of the nuclear beta-catenin in spindle cell and pleomorphic sarcomas. A possible association between beta-catenin accumulation and spindle cell morphogenesis may exist in SS.

摘要

软组织肉瘤(STSs)中的细胞核β-连环蛋白染色已被证明与通过增殖活性评估的肿瘤进展或不良预后相关。滑膜肉瘤(SS)中也显示Wnt信号通路频繁激活,表明该通路在SS中具有特定作用。我们研究了软组织肉瘤中细胞核β-连环蛋白染色的作用。免疫组织化学检测细胞核β-连环蛋白积累与纺锤状细胞和多形性肉瘤中细胞周期蛋白D1过表达相关(P = 0.037),并且这些蛋白的表达均匀分布在每个切片中。在某些情况下,在高度多形性和有丝分裂的细胞中观察到强β-连环蛋白细胞核染色。此外,与没有细胞核β-连环蛋白积累的肿瘤相比,有细胞核β-连环蛋白积累的肿瘤显示细胞周期蛋白D1 mRNA表达水平有统计学意义的增加(P = 0.023)。细胞周期蛋白D1过表达的肿瘤中细胞周期蛋白D1 mRNA表达水平在统计学上高于没有过表达的肿瘤(P = 0.037),表明细胞周期蛋白D1过表达是由于转录激活。然而,在SS中未检测到这些相关性。在双相性SS中,在纺锤状细胞中观察到β-连环蛋白细胞核染色,而在β-连环蛋白保持膜性表达的腺管区域中观察到细胞周期蛋白D1细胞核染色。在这一系列病例中,β-连环蛋白基因第3外显子和腺瘤性息肉病大肠杆菌基因突变簇区域未发生突变。因此,细胞周期蛋白D1可被视为纺锤状细胞和多形性肉瘤中细胞核β-连环蛋白的靶标之一。在SS中可能存在β-连环蛋白积累与纺锤状细胞形态发生之间的关联。

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