Skp2 protein expression in soft tissue sarcomas
Skp2 protein expression in soft tissue sarcomas
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DOI：
10.1200/jco.2003.05.112
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发表时间：
2003-02-15
影响因子：
45.3
通讯作者：
Lloyd, RV
中科院分区：
文献类型：
--
作者：
Oliveira, AM;Okuno, SH;Lloyd, RV
背景：p45 S 期激酶相关蛋白 2 (p45(skp2)) 是 F-box 蛋白家族的成员，是 Skp1-Cullin-F-box 蛋白 (SCF) 泛素连接酶复合物 (SCFskp2) 的重要组成部分。后者与 p27(kip1) (p27) 和 G(1)-S 细胞周期进程的泛素化和降解有关。 Skp2在大量软组织肉瘤中的表达和预后作用尚未被研究。方法：2例软组织肉瘤（美国癌症联合委员会II期和III期）的临床病理特征和Skp2、p27和Ki-67蛋白的免疫组织化学表达。采用Kaplan-Meier法和Cox回归模型进行生存分析。结果：男女比例为1.2：1，诊断时中位年龄为53岁。肿瘤主要位于下肢（n = 163；90%），中位大小为 9 cm。在 68 个肿瘤 (37%) 中发现了高 Skp2 表达（大于或等于 10% 的细胞），并且与高级别组织学 (P = .002) 和 Ki-67 增殖指数 (r = 0.44; P < .0001) 相关，但与 p27 表达无关 (r = -0.02; P = .80)。通过单变量分析，Skp2 高表达与无转移、无病和总生存率降低相关。在多变量模型中，Skp2 高表达是局部无复发、无病和总生存率降低的独立预测因子。结论：这些结果表明 Skp2 表达与软组织肉瘤中的细胞增殖和较差的预后相关。 Skp2 和 p27 之间缺乏负相关表明与 Skp2 表达或 p27 蛋白水解相关的其他分子事件可能在这些肿瘤中起作用。 (C) 2003 年，美国临床肿瘤学会。
Background: p45 S phase kinase-associated protein-2 (p45(skp2)), a member of the F-box family of proteins, is an important component of the Skp1-Cullin-F-box protein (SCF) ubiquitin-ligase complex (SCFskp2). The latter has been implicated in the ubiquitination and degradation of p27(kip1) (p27) and G(1)-S cell cycle progression. The expression and prognostic role of Skp2 in a large series of soft tissue sarcomas has not been previously investigated.Methods: Clinicopathologic features and immunohistochemical expression of Skp2, p27, and Ki-67 proteins were 2 cases of soft tissue sarcomas (American Joint Committee on Cancer stages II and III). Survival analyses were performed using the Kaplan-Meier method and the Cox regression model.Results: The male to female ratio was 1.2:1, and the median age at the diagnosis was 53 years. The tumors were predominantly located in the lower extremities (n = 163; 90%) and had a median size of 9 cm. High Skp2 expression (greater than or equal to 10% of the cells) was identified in 68 tumors (37%), and was correlated with high grade histology (P = .002) and Ki-67 proliferative index (r = 0.44; P < .0001), but not with p27 expression (r = -0.02; P = .80). By univariate analysis, high Skp2 expression was associated with decreased metastasis-free, disease-free, and overall survival. In a multivariate model, high Skp2 expression was an independent predictor for decreased local recurrence-free, disease-free, and overall survival.Conclusion: These results indicate that Skp2 expression is associated with cell proliferation and a worse prognosis in soft tissue sarcomas. The lack of an inverse correlation between Skp2 and p27 suggests that additional molecular events associated with either Skp2 expression or p27 proteolysis may be operating in these tumors. (C) 2003 by American Society of Clinical Oncology.