Seki Ritsuko, Okamura Takashi, Koga Hironori, Yakushiji Kazuaki, Hashiguchi Michitoshi, Yoshimoto Kohji, Ogata Hideaki, Imamura Rie, Nakashima Yutaka, Kage Masayoshi, Ueno Takato, Sata Michio
Second Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan.
Am J Hematol. 2003 Aug;73(4):230-5. doi: 10.1002/ajh.10379.
The F-box protein Skp2 positively regulates the G1-S transition by promoting degradation of the cyclin-dependent kinase inhibitor p27(kip1) (p27). Recent evidence has suggested an oncogenic role of Skp2 in not only carcinogenesis but also lymphomagenesis. In this study, we performed immunohistochemical analysis on the cell-cycle-associated proteins, Skp2, p27, and Ki-67, in 27 patients with de novo diffuse large B-cell lymphoma (DLBCL), evaluating the correlation between the clinical characteristics and expression levels of these proteins. The patients were classified into two groups according to the positivity for Skp2 expression: a high Skp2 expression group (>60% positive for Skp2 in lymphoma cells) and a low Skp2 expression group (< or = 60%). A high level of Skp2 expression significantly correlated with advanced clinical stage (P = 0.029), although the increase did not correlate with age, gender, LDH levels, presence of extranodal disease, or performance status and resulted in no correlation with the International Prognostic Index-based risk grading. However, it was noteworthy that the high Skp2 expression group demonstrated a significantly worse prognosis than the low Skp2 expression group (P = 0.0007). The expression level of Skp2 correlated with that of Ki-67 but not necessarily with that of p27. The p27 expression level did not correlate patients' prognosis. Taken together, it was suggested that Skp2 was a valuable and independent marker predicting the outcome in DLBCL.
F-box蛋白Skp2通过促进细胞周期蛋白依赖性激酶抑制剂p27（kip1）（p27）的降解来正向调节G1-S期转换。最近的证据表明，Skp2不仅在致癌过程中，而且在淋巴瘤发生过程中都具有致癌作用。在本研究中，我们对27例初发弥漫性大B细胞淋巴瘤（DLBCL）患者的细胞周期相关蛋白Skp2、p27和Ki-67进行了免疫组化分析，评估这些蛋白的临床特征与表达水平之间的相关性。根据Skp2表达的阳性情况将患者分为两组：Skp2高表达组（淋巴瘤细胞中Skp2阳性率>60%）和Skp2低表达组（≤60%）。Skp2高表达水平与晚期临床分期显著相关（P = 0.029），尽管其升高与年龄、性别、乳酸脱氢酶水平、结外病变的存在或体能状态无关，且与基于国际预后指数的风险分级无关。然而，值得注意的是，Skp2高表达组的预后明显比Skp2低表达组差（P = 0.0007）。Skp2的表达水平与Ki-67的表达水平相关，但不一定与p27的表达水平相关。p27的表达水平与患者的预后无关。综上所述，提示Skp2是预测DLBCL预后的一个有价值的独立标志物。
