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肝细胞生长因子与c-Met原癌基因产物在滑膜肉瘤中的共表达。

Coexpression of hepatocyte growth factor and c-Met proto-oncogene product in synovial sarcoma.

作者信息

Motoi T, Ishida T, Kuroda M, Horiuchi H, Oka T, Matsumoto K, Nakamura T, Machinami R

机构信息

Department of Pathology, Faculty of Medicine, University of Tokyo, Japan.

出版信息

Pathol Int. 1998 Oct;48(10):769-75. doi: 10.1111/j.1440-1827.1998.tb03836.x.

DOI:10.1111/j.1440-1827.1998.tb03836.x
PMID:9788260
Abstract

Hepatocyte growth factor (HGF) is a heterodimeric polypeptide growth factor that has pleiotropic roles, including those of mitogen, motogen and morphogen. The HGF receptor is characterized as a c-Met proto-oncogene product (c-Met), which is a heterodimeric tyrosine kinase receptor. Hepatocyte growth factor acts as a mediator between the mesenchymal and epithelial tissues because HGF is produced by mesenchymal cells and c-Met is mainly expressed on various epithelial cells. Furthermore, the HGF/c-Met system plays an important role in embryogenesis and the regeneration of various organs. Synovial sarcoma (SS) are unique sarcoma that show epithelial differentiation, but little is known about their histogenesis. The expression of HGF and c-Met was examined by immunohistochemistry in SS specimens from 12 patients (six each of biphasic and monophasic fibrous types). Immunohistochemical coexpression of HGF and c-Met was demonstrated in the epithelial component of five biphasic SS, while only c-Met was expressed in the epithelioid nests of three monophasic fibrous SS. The spindle cell component was negative for HGF and c-Met. In SS, positivity for epithelial markers, such as cytokeratins and epithelial membrane antigen, was diffusely observed in the epithelial component and was focally observed in spindle cells, while vimentin was positive predominantly in the spindle cell component. The areas expressing HGF and c-Met corresponded to distinct epithelial structures; however, HGF and c-Met expression were not found in any other tumor cells expressing epithelial markers in the spindle cell component of SS. Considering the morphogenic effect of HGF, which has been known to be one of its most important roles, the unique immunohistochemical localization of HGF and c-Met in SS suggests that the HGF/c-Met system may be closely related to the formation of epithelial (glandular) structures in biphasic SS.

摘要

肝细胞生长因子(HGF)是一种异二聚体多肽生长因子,具有多种作用,包括有丝分裂原、促动素和形态发生素的作用。HGF受体的特征是c-Met原癌基因产物(c-Met),它是一种异二聚体酪氨酸激酶受体。肝细胞生长因子作为间充质组织和上皮组织之间的介质,因为HGF由间充质细胞产生,而c-Met主要在各种上皮细胞上表达。此外,HGF/c-Met系统在胚胎发生和各种器官的再生中起重要作用。滑膜肉瘤(SS)是一种独特的肉瘤,表现出上皮分化,但其组织发生知之甚少。通过免疫组织化学检测了12例患者(双相型和单相纤维型各6例)SS标本中HGF和c-Met的表达。在5例双相型SS的上皮成分中证实了HGF和c-Met的免疫组织化学共表达,而在3例单相纤维型SS的上皮样巢中仅表达c-Met。梭形细胞成分中HGF和c-Met呈阴性。在SS中,上皮标志物如细胞角蛋白和上皮膜抗原的阳性在其上皮成分中弥漫性观察到,在梭形细胞中局灶性观察到,而波形蛋白主要在梭形细胞成分中呈阳性。表达HGF和c-Met的区域对应于不同的上皮结构;然而,在SS梭形细胞成分中表达上皮标志物的任何其他肿瘤细胞中均未发现HGF和c-Met表达。考虑到HGF已知的最重要作用之一即形态发生作用,HGF和c-Met在SS中独特的免疫组织化学定位表明HGF/c-Met系统可能与双相型SS中上皮(腺)结构的形成密切相关。

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Tyrosine kinase inhibitors in treating soft tissue sarcomas: sunitinib in non-GIST sarcomas.酪氨酸激酶抑制剂治疗软组织肉瘤:舒尼替尼在非 GIST 肉瘤中的应用。
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