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滑膜肉瘤中细胞凋亡的预后意义:与临床病理参数、细胞增殖活性及凋亡相关蛋白表达的相关性

Prognostic significance of apoptosis in synovial sarcoma: correlation with clinicopathologic parameters, cell proliferative activity, and expression of apoptosis-related proteins.

作者信息

Kawauchi S, Fukuda T, Oda Y, Saito T, Oga A, Takeshita M, Yokoyama K, Chuman H, Iwamoto Y, Sasaki K, Tsuneyoshi M

机构信息

Department of Pathology, National Kyushu Cancer Center, Fukuoka, Japan.

出版信息

Mod Pathol. 2000 Jul;13(7):755-65. doi: 10.1038/modpathol.3880131.

DOI:10.1038/modpathol.3880131
PMID:10912935
Abstract

bcl-2 overexpression in synovial sarcomas has been recently reported. Although it is widely known that bcl-2 suppresses apoptosis in various cells, there are no studies that have examined the significance of apoptosis in synovial sarcoma. In the present study, we visualized apoptotic tumor cells by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick end-labeling (TUNEL) method in 49 cases of primary synovial sarcoma. The degree of apoptosis was analyzed in relation to several clinicopathologic parameters, cell proliferative activity, and immunohistochemical expression of apoptosis-related proteins, including bcl-2, bax, bcl-x, bak, p53, p21 (WAF1/CIP1), Fas, and Fas ligand. TUNEL index (TUNEL-I) significantly correlated with the mitotic index (MI) (ñ = 0.60, P < .0001) and Ki-67 labeling index (MIB1-I) (ñ = 0.52, P = 0.0005). There was a highly significant association between high TUNEL-I value (>.8%) and poor prognosis (log-rank test; P < .0001). Many synovial sarcomas were diffusely positive for bcl-2 family proteins (bcl-2, bax, bcl-x, and bak) and were negative or only sporadically positive for Fas, Fas ligand, p53, and p21 (WAF1/CIP1) proteins. The results indicated that increased rate of apoptosis in primary synovial sarcoma was considered to be an indicator of poor prognosis. In addition, apoptosis in synovial sarcoma may be controlled by multiple apoptosis-regulating mechanisms, including the bcl-2 family.

摘要

最近有报道称滑膜肉瘤中存在bcl - 2过表达。尽管众所周知bcl - 2可抑制多种细胞的凋亡,但尚无研究探讨凋亡在滑膜肉瘤中的意义。在本研究中,我们采用末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸原位缺口末端标记法(TUNEL法)对49例原发性滑膜肉瘤中的凋亡肿瘤细胞进行了可视化分析。分析了凋亡程度与多种临床病理参数、细胞增殖活性以及凋亡相关蛋白(包括bcl - 2、bax、bcl - x、bak、p53、p21(WAF1/CIP1)、Fas和Fas配体)的免疫组化表达之间的关系。TUNEL指数(TUNEL - I)与有丝分裂指数(MI)显著相关(r = 0.60,P <.0001),与Ki - 67标记指数(MIB1 - I)也显著相关(r = 0.52,P = 0.0005)。高TUNEL - I值(>.8%)与预后不良之间存在高度显著的关联(对数秩检验;P <.0001)。许多滑膜肉瘤对bcl - 2家族蛋白(bcl - 2、bax、bcl - x和bak)呈弥漫性阳性,而对Fas、Fas配体、p53和p21(WAF1/CIP1)蛋白呈阴性或仅散在阳性。结果表明,原发性滑膜肉瘤中凋亡率增加被认为是预后不良的一个指标。此外,滑膜肉瘤中的凋亡可能受多种凋亡调节机制控制,包括bcl - 2家族。

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