Fang Fu-Min, Chien Chih-Yen, Li Chien-Feng, Shiu Wan-Yu, Chen Chang-Han, Huang Hsuan-Ying
Department of Radiation Oncology, Kaohsiung Chang Gung Head and Neck Oncology Group, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Int J Radiat Oncol Biol Phys. 2009 Jan 1;73(1):202-7. doi: 10.1016/j.ijrobp.2008.04.008. Epub 2008 Jun 4.
The S-phase kinase-associated protein 2 (Skp2) oncoprotein is an E3 ubiquitin ligase targeting the p27(Kip1) tumor suppressor for degradation. We evaluated the prognostic utility of Skp2 in nasopharyngeal carcinoma (NPC), with an emphasis on distant metastasis-free (DMF) survival.
Immunohistochemical expression of Skp2 was assessed by H-score for 233 NPC patients without initial distant metastasis and correlated with the clinicopathologic features, therapeutic modalities, locoregional control rate, DMF survival, and overall survival (OS). No selection bias in essential parameters was shown between these and another 113 control patients.
Skp2 was detectable in most patients (95%) but displayed a wide range of expression. Despite no correlation between Skp2 and any clinicopathologic factor, greater Skp2 expression (H-score >80) significantly portended inferior DMF survival (p = 0.01) and OS (p = 0.02) when categorically dichotomizing the study cohort. The associations with DMF survival (p = 0.003) and OS (p = 0.003) became even stronger when the H-score was expressed as a continuous variable. In the multivariate model, greater Skp2 expression remained significantly predictive of poorer DMF survival and OS (p = 0.01 for both), along with T stage (p = 0.04 for DMF survival; p = 0.005 for OS), N stage (p = 0.008 for DMF survival; p = 0.02 for OS), and/or age (p = 0.001 for OS). In contrast, T stage (p = 0.01) was the single independent prognosticator of LCR.
The results of our study have shown that Skp2 expression is frequent in NPC and has a wide range of distribution in H-score. Skp2 overexpression is significantly predictive of DMF survival and OS, independent of the T stage and/or older age. Therefore, Skp2 might represent a useful prognostic adjunct to risk stratify NPC patients for appropriate allocation of adjuvant therapy.
S期激酶相关蛋白2（Skp2）癌蛋白是一种E3泛素连接酶，可靶向降解p27（Kip1）肿瘤抑制因子。我们评估了Skp2在鼻咽癌（NPC）中的预后价值，重点是无远处转移（DMF）生存期。
通过H评分评估233例无初始远处转移的NPC患者Skp2的免疫组化表达，并将其与临床病理特征、治疗方式、局部区域控制率、DMF生存期和总生存期（OS）相关联。在这些患者与另外113例对照患者之间，未显示出基本参数存在选择偏倚。
大多数患者（95%）可检测到Skp2，但表达范围较广。尽管Skp2与任何临床病理因素均无相关性，但当对研究队列进行二分法分类时，较高的Skp2表达（H评分>80）显著预示着较差的DMF生存期（p = 0.01）和OS（p = 0.02）。当H评分作为连续变量时，其与DMF生存期（p = 0.003）和OS（p = 0.003）的关联更强。在多变量模型中，较高的Skp2表达仍然显著预测较差的DMF生存期和OS（两者均为p = 0.01），同时还有T分期（DMF生存期p = 0.04；OS p = 0.005）、N分期（DMF生存期p = 0.008；OS p = 0.02）和/或年龄（OS p = 0.001）。相比之下，T分期（p = 0.01）是局部区域控制率的唯一独立预后因素。
我们的研究结果表明，Skp2表达在NPC中很常见，且在H评分中分布范围较广。Skp2过表达显著预测DMF生存期和OS，独立于T分期和/或年龄。因此，Skp2可能是一种有用的预后辅助指标，用于对NPC患者进行风险分层，以便合理分配辅助治疗。
