前列腺癌中泛素降解途径蛋白的表达及与临床病理特征的相关性

目的 探讨泛素降解途径蛋白Skp2、p27kipl和PTEN在前列腺癌中的表达及与前列腺癌各项临床病理特征的关系,并探讨三者的相关性.方法 应用免疫组织化学法和图像分析系统研究41例前列腺癌标本、20例开放手术切除良性前列腺增生标本中Skp2、p27kipl和PTEN的表达情况.并使用Mann-Whitney检验、Spearman等级相关分析临床病理资料与免疫组化的结果及Skp2、p27kipl和PTEN之间的相关性.结果 在前列腺癌中,Skp2蛋白染色阳性率显著高于良性前列腺增生(P<0.001),p27kipl蛋白染色阳性率显著低于良性前列腺增生(P<0.001),PTEN蛋白染色阳性率显著低于良性前列腺增生(P<0.001).Skp2 蛋白表达与前列腺癌术前PSA水平、肿瘤穿透前列腺被膜、肿瘤分期、病理分级密切相关(P<0.05).而p27kipl和PTEN蛋白表达与上述临床病理特征负相关(P<0.05).Spearman 等级相关分析表明,Skp2与p27kipl蛋白表达呈负相关(r=-0.572, P<0.001),Skp2与PTEN 蛋白表达呈负相关(r=-0.433, P=0.005).结论 Skp2蛋白在前列腺癌中表达增加,与术前PSA水平、局部浸润、临床分期和病理分级呈正相关,而p27蛋白在前列腺癌中表达降低,与上述临床病理特征呈负相关,Skp2蛋白表达与p27蛋白表达之间呈负相关.Skp2表达与抑癌基因PTEN蛋白表达呈负相关.     

乳腺导管内增生性病变中Skp2和p27kip1的表达及意义

目的从蛋白水平研究导管内增生性病变中Skp2和p27kip1表达异常与乳腺癌发生之间的相关性。方法采用免疫组织化学法分别检测120例导管内增生性病变,包括普通型导管上皮增生(usualductal hyperplasia,UDH),平坦型上皮不典型性病变(flat epithelial atypia,FEA),不典型导管上皮增生(atypical ductal hyperplasia,ADH),导管原位癌(ductal carcinoma in situ,DCIS)各30例石蜡包埋组织,以及健康对照组中Skp2和p27kip1蛋白表达水平,分析比较四组病变中Skp2和p27kip1蛋白阳性表达率以及这两种蛋白表达的相关性。结果四个亚型Skp2蛋白阳性表达率均高于健康对照组(P<0.05),DCIS组、ADH组和FEA组Skp2蛋白阳性表达率均高于UDH组(P<0.05),DCIS组Skp2蛋白阳性表达率高于ADH组和FEA组(P<0.05);p27kip1蛋白在UDH组、FEA组、ADH组、DCIS组的阳性表达率均低于健康对照(P<0.05),p27kip1蛋白在DCIS组阳性表达率低于UDH组、ADH组和FEA组(P<0.05)。Skp2与p27kip1阳性细胞率在四组导管内增生性病变中的蛋白表达阳性率总体上呈负相关(r=-0.411,P=0.000)。在UDH组与DCIS组内Skp2与p27kip1表达均呈负相关(r=-0.406,P=0.026;r=-0.544,P=0.002)。结论 Skp2蛋白表达水平升高p27kip1蛋白水平下降与乳腺导管上皮不典型增生和乳腺癌发生相关。     

pAkt、Skp2和P27kip1蛋白在肝细胞癌中的表达及意义

目的探讨人肝细胞癌组织中pAkt、Skp2和P27kip1蛋白的表达及其临床意义。方法应用免疫组织化学方法检测78例肝细胞癌及21例正常肝组织中pAkt、Skp2和P27kip1蛋白的表达,分析其与肝细胞癌临床病理特征及预后的关系。结果肝细胞癌组织中pAkt及Skp2蛋白的高表达率分别为43.6%和47.4%,显著高于正常肝组织(P＜0.05),P27kip1蛋白的阳性表达率为34.6%,显著低于正常肝组织(P＜0.05)。pAkt蛋白的表达与肿瘤直径、侵犯周围脏器或淋巴结转移及TNM分期有关(P＜0.05);Skp2蛋白的表达与肿瘤直径、门静脉癌栓及TNM分期有关(P＜0.05);P27kip1蛋白的表达与肿瘤直径、数目及TNM分期有关(P＜0.05)。Skp2与pAkt蛋白表达呈正相关(r=0.356,P=0.001),与P27kip1蛋白表达呈负相关 (r=-0.313, P=0.005)。pAkt、Skp2蛋白高表达患者术后生存率明显低于低表达患者(P=0.000),P27kip1蛋白的表达与患者术后生存率无关。Cox模型多因素分析结果显示,TNM分期、pAkt及Skp2蛋白的表达是影响肝细胞癌预后的独立因素。结论肝细胞癌组织中pAkt、Skp2及P27kip1蛋白的表达失调与肝细胞癌的恶性生物学行为密切相关,pAkt及Skp2可以作为评价患者预后的指标。     

良性前列腺增生及前列腺癌的ADC值与PAP、P504S、PSA表达的相关性研究

目的：探讨良性前列腺增生和前列腺癌的ADC值与前列腺相关标志物PAP、P504S、PSA表达的关系。方法收集经病理证实的65例前列腺疾病患者,其中良性前列腺增生30例,前列腺癌35例。病理检查前3个月内均行前列腺MRI、DWI检查,采用单次激发EPI序列,b值为0 s/mm2和800 s/mm2,并采用免疫组化检测组织标本中PAP、P504S、PSA的表达,分析ADC值与PAP、P504S、PSA表达的关系。结果良性前列腺增生和前列腺癌的ADC值分别为（1.73±0.21）×10-3 mm2/s和（1.34±0.15）×10-3 mm2/s,差异具有统计学意义（t=8.545,P=0.000）。PAP和PSA在良性前列腺增生和前列腺癌中均表达,差异无统计学意义（P均＞0.05）,P504S在前列腺癌中的表达显著高于良性增生（Z=-7.055,P=0.000）,双变量相关分析显示ADC值与P504S的表达呈显著负相（Spearman's相关系数r=-0.654,P=0.000）;结论 PAP和PSA不能区别前列腺良恶性病变;P504S可以作为前列腺癌标志物;ADC值可以定量评价良性前列腺增生和前列腺癌,且与P504S存在负相关,可以作为前列腺良恶性病变MRI诊断的参考指标。     

Skp2在急性白血病中的表达及其与p27(kip1)和Ki67的关系

 目的 探讨S期激酶相关蛋白2（Skp2）在急性白血病中的表达及其与p27（kip1）蛋白和增生相关抗原Ki67的关系。方法 采用免疫细胞化学法检测三者在初治急性非淋巴细胞白血病患者、急性淋巴细胞白血病患者及正常对照者骨髓单个核细胞中的表达。结果 初治急性白血病患者中Skp2和Ki67的表达水平明显高于对照组（均P＜0.01）,p27（kip1）的表达水平明显低于对照（P＜0.05）,以上各指标在急性非淋巴细胞白血病和急性淋巴细胞白血病之间差异无统计学意义（P＞0.05）,且Skp2与p27（kip1）、Ki67的表达分别呈负相关（r s = -0.489,P＜0.05）、正相关（r s = 0.609,P＜0.01）。结论 Skp2异常增高可能通过促进p27（kip1）的降解而参与了白血病的发生,并与细胞增生相关抗原Ki67正相关     

Skp2与p27kip1在人子宫颈鳞癌中的表达及其与HPV感染的关系

目的 S期激酶相关蛋白2 (S-phase kinase-associated protein 2,Skp2)与p27 kip1在人子宫颈鳞癌中的表达及其与人乳头瘤病毒(human papilloma virus,HPV)感染的关系.方法 选取子宫颈鳞状细胞癌(squamous cell carcinoma of cervix,SCC)组织50例、子宫颈上皮内瘤样病变(cervical intraepithelial neoplasias,CINs)组织40例,并选取慢性子宫颈炎(chronic cervicitis,CC)组织15例为对照组.用免疫组织化学法检测p27 kip1和Skp2的表达情况,并与临床病理特征进行比较;用原位杂交法检测HPV 16/18的表达,及其与Skp2和p27kip1表达的相关性.结果 50例SCC组织中Skp2蛋白表达阳性率为76.0％,高于CC(13.3％,P＜0.01)及CINs(57.5％,P＜0.05)组织;p27kip1 蛋白在SCC组织中表达阳性率为24.0％,低于CC (92.6％,P＜0.01)及CINs(52.5％,P＜0.05)组.Skp2和 p27“p1的表达在淋巴结转移方面差异有统计学意义(P＜0.05),而在年龄、分化程度、临床分期方面差异均无统计学意义(均P＞0.05).子宫颈鳞癌组织中HPV 16/18 DNA表达阳性率为74.0％,高于CC组的13.3％,组间差异有统计学意义(P＜0.01);但与CINs组表达阳性率(62.5％)比较差异无统计学意义(P＞0.05).HPV 16/18感染与Skp2蛋白表达之间呈正相关(r=0.238,P＜0.05),HPV 16/18感染与p27 kip1蛋白表达之间呈负相关(r=-0.245,P＜0.05).结论 Skp2的高表达和p27 kip1蛋白低表达与子宫颈鳞癌的发生、转移以及与HPV感染有密切关系.     

胃癌组织Skp2表达的意义及与p27表达的关系

目的探讨人胃癌S期激酶相关蛋白2(S-phase k inase-assoc iated prote in 2,Skp2)表达的意义及与p27表达的关系。方法采用免疫组化方法检测138例原发性胃癌,配对癌旁胃黏膜,102例配对淋巴结转移胃癌组织,30例非典型增生,30例肠上皮化生(肠化),10例慢性浅表性胃炎和5例正常胃黏膜Skp2的表达及138例原发性胃癌p27的表达。结果Skp2表达的阳性率(%),肠化(12.68±0.86)及癌旁胃黏膜(19.32±1.22)均明显高于慢性浅表性胃炎(0.53±0.13)及正常胃黏膜(0.47±0.19)(P=0.000),后两者差异无显著性(P=0.716);非典型增生(16.74±0.82)明显高于肠化(P=0.000);原发性胃癌(31.34±2.17)明显高于非典型增生及癌旁胃黏膜(P值均=0.000);淋巴结转移胃癌组织(39.76±2.00)明显高于原发性胃癌(P=0.037)。胃癌Skp2的阳性率与分化程度(rho=0.315,P=0.000)、脉管内瘤栓(rho=0.303,P=0.000)及淋巴结转移(rho=0.254,P=0.000)呈正相关。胃癌Skp2表达与靶蛋白p27表达呈负相关(rho=-0.451,P=0.000)。结论Skp2蛋白过表达与胃癌的发生及转移有关;胃癌Skp2蛋白过表达与p27蛋白降解有关,提示Skp2蛋白过表达在胃癌发生、发展过程中可能起重要作用。     

胃癌中Cks1、P27Kip1、Skp2蛋白表达相关性及其意义

目的:探讨Cks1在胃癌发生及Skp2调节P27Kip1降解过程中的作用。方法:应用流式细胞术检测正常胃黏膜、胃不典型增生组织及胃癌组织中Cks1、P27Kip1、Skp2蛋白的表达。结果:由正常胃黏膜、胃不典型增生组织到胃癌中Cks1、Skp2的表达均呈上升趋势(P<0.05),P27Kip1表达则呈下降趋势(P<0.05)。胃癌中Cks1、Skp2表达均与P27Kip1表达呈负相关(r=-0.649,P<0.05;r=-0.732,P<0.05);而Cks1蛋白表达与Skp2蛋白无相关性(P>0.05)。胃癌中Cks1表达与肿瘤分化程度相关(P<0.05),而与肿瘤浸润深度、淋巴结转移及临床分期不相关(P>0.05)。结论:Cks1可能参与胃癌的发生;胃癌中Cks1可能参与Skp2调节P27Kip1泛素化的降解过程。     

Skp2与P27bpi在基底细胞癌及其临床病理特征中的表达

目的 检测S期激酶相关蛋白2（Skp2）与激酶抑制蛋白1（P27kip1）在基底细胞癌（BCC）中的表达,进而探明两者在BCC发生发展中的作用及其相关性,以及与临床病理特征的关系,并初步探讨Skp2与P27kip1在BCC 临床分型中的作用,尤其在硬化型中的作用.方法用免疫组织染色SP两步法检测50例BCC及30例正常皮肤组织中Skp2与P27kip1的表达情况,并结合患者的年龄、性别及临床分型等进行综合分析.结果 Skp2定位于胞核或胞质,而P27kip1只定位于胞核.Skp2在BCC中呈高表达,而P27kip1呈低表达,与正常皮肤组织对照组比较,差异有统计学意义（P＜0.05）.Skp2和P27kip1的异常表达与BCC的临床分型有关（P＜0.05）,而与患者性别、年龄等因素均无关（P＞0.05）.在BCC中,Skp2的阳性表达与P27kip1的阳性表达呈负相关（r=-0.624;P＜0.05）;但在BCC的硬化型中,两者无相关性（P＞0.05）.结论 Skp2与P27kip1在BCC中的阳性表达呈负相关,提示在BCC的发生及发展中两者可能起协同作用,并可能为将来的治疗提供靶点.Skp2在硬化型BCC组的表达高于结节型及浅表型BCC组,而P27kip1则相反,提示Skp2与P27kip1可能参与皮肤BCC的分型,且可能成为BCC分型的预测因子,从而为不同类型BCC手术切缘的设计提供生化指标依据.     

前列腺癌与增生组织雄激素受体基因微卫星多态性的研究

目的探讨雄激素受体基因CAG微卫星多态性与前列腺癌以及前列腺增生的关系.方法运用聚合酶链反应-单链构象多态性分析法(PCR-SSCP),对18例良性前列腺增生、37例前列腺腺癌组织进行雄激素受体基因CAG微卫星数量测定.结果良性前列腺增生、B期、C～D期前列腺癌、高分化、中分化以及低分化前列腺癌的雄激素受体基因CAG均数分别是26.11±3.35、25.04±1.88、22.14±2.64、25.6±1.36、24.29±3.19和23.64±2.64.其均数比较,良性前列腺增生与C～D期前列腺癌以及低分化前列腺癌间差异有显著性(P=0.001～0.016),良性前列腺增生与B期前列腺癌、中分化及高分化前列腺癌其差异无显著性(P=0.249～0.636).结论雄激素受体基因CAG微卫星数量的差异性可能与良性前列腺增生以及不同类型前列腺癌的发病机制相关.     

胃癌组织Skp2表达的意义及其与P27、PTEN表达的关系

背景与目的:S期激酶相关蛋白2(S-phaseKinase-associatedProtein2,Skp2)促进泛素介导的细胞周期素依赖激酶抑制剂P27蛋白降解,是细胞G1-S期转化所必需。研究发现Skp2过表达参与细胞转化和肿瘤的形成。本研究旨在探讨人胃癌Skp2表达的意义及Skp2与P27和PTEN表达的关系。方法:采用免疫组化法检测胃癌组织及配对癌旁胃粘膜138例、配对淋巴结转移癌组织102例、非典型增生30例、肠上皮化生30例、慢性浅表性胃炎10例和正常胃粘膜5例Skp2表达及138例胃癌P27和PTEN的表达。结果:Skp2的标记率(%)在肠化(12.68±0.86)及癌旁胃粘膜(19.32±1.22)均明显高于慢性浅表性胃炎(0.53±0.13)及正常胃粘膜(0.47±0.19)(P<0.001),后两者无显著性差异(P﹥0.05);非典型增生(16.74±0.82)明显高于肠化(P<0.001);原发胃癌(31.34±2.17)明显高于非典型增生及癌旁胃粘膜(P<0.001);淋巴结转移胃癌组织(39.76±2.00)明显高于原发胃癌(P=0.037)。胃癌Skp2标记率与分化程度(rs=0.315,P=0.000)、脉管内瘤栓(rs=0.303,P=0.000)及淋巴结转移(rs=0.254,P=0.000)呈正相关。胃癌Skp2表达与靶蛋白P27表达(rs=-0.451,P=0.000)和肿瘤抑制蛋白PTEN(rs=-0.480,P=0.000)表达呈负相关;胃癌PTEN表达与P27表达呈正相关(rs=0.642,P=0.000)。结论:胃癌Skp2蛋白过表达与P27蛋白降解及PTEN蛋白低表达有关,提示Skp2蛋白过表达可能是胃癌发生和发展的一个重要原因。     

Elevated Skp2 protein expression in human prostate cancer: association with loss of the cyclin-dependent kinase inhibitor p27 and PTEN and with reduced recurrence-free survival.

The F-box protein Skp2 (Fbl1) is a positive regulator of G1-S transition and promotes ubiquitin-mediated proteolysis of the cyclin-dependent kinase inhibitor p27. Its overexpression has been implicated in cell transformation and oncogenesis in both in vitro and in vivo models. In this study, we investigated its role in human prostate cancer progression. Immunohistochemical analysis was performed on formalin-fixed paraffin sections of 622 radical prostatectomy specimens, 74 prostatic intraepithelial neoplasm specimens, as well as in 4 normal prostate organ donors assembled into tissue microarrays. We found that both luminal and basal epithelial cells in normal prostate had very low Skp2 levels, but Skp2 levels and labeling frequency increased dramatically in both premalignant lesions of prostatic intraepithelial neoplasm (P = 0.0252) and in prostate cancer (P = 0.0037). The Skp2 labeling frequency in cancer was positively correlated with preoperative serum prostate-specific antigen level (P = 0.0499) and Gleason score (P = 0.0002), whereas the Skp2 index was positively correlated with extraprostatic extension (P = 0.0454), clinical stage (P = 0.0170), as well as Gleason score (P = 0.0002). Kaplan-Meier analysis revealed that a higher Skp2 labeling index (>10) was a significant predictor of shorter biochemical recurrence-free survival time after radical prostatectomy (P < 0.0363, log-rank test). An inverse correlation of Skp2 was observed with both its biochemical target p27 expression in prostate cancer (P = 0.0003) and with its putative negative regulator, the PTEN tumor suppressor protein (P = 0.0444). These data suggest that induction of Skp2 may be causally linked with decreased levels of p27 in prostate cancer and implicate PTEN in the regulation of Skp2 expression in vivo, as previous tissue culture experiments have suggested.     

非小细胞肺癌组织中Skp2的表达及其与p27kip1和Ki-67蛋白表达的关系

目的:探讨Skp2的表达在非小细胞肺癌(nonsmallcelllungcancer,NSCLC)发生发展中的作用,及其与p27kip1和Ki67蛋白表达的关系。方法:应用免疫组化SP法检测Skp2、p27kip1和Ki67三种蛋白在60例NSCLC和20例正常支气管黏膜上皮组织中的表达。结果:NSCLC组织中Skp2蛋白表达的阳性率为48.33%(29/60),显著高于正常支气管黏膜上皮组织中的表达,P=0.000。Skp2的表达与肿瘤的组织学类型、肿瘤细胞的分化程度、TNM分期、淋巴结转移和患者吸烟与否显著相关,P值分别为0.038、0.005、0.019、0.010和0.002,但与患者的年龄及性别无关,P值分别为0.833和0.281。NSCLC组织中Skp2表达与p27kip1表达呈显著负相关,P=0.001;而与Ki67表达呈显著正相关,P=0.027。结论:Skp2在NSCLC组织中表达是上调的,可能是通过作用于细胞周期调控蛋白p27kip1,加速了对p27kip1泛素化依赖的蛋白降解,使其表达及代谢发生异常,导致细胞周期失控并促进细胞异常增殖,从而参与了NSCLC的发生和发展。     

S-phase kinase-associated protein 2 expression in laryngeal squamous cell carcinomas and its prognostic implications

The F-box protein S-phase kinase-associated protein 2 (Skp2) positively regulates the G1-S transition by controlling the stability of several G1 regulators, such as the cell cycle inhibitor p27kip1. However, the clinical significance of Skp2 in patients with laryngeal squamous cell carcinoma (LSCC) remains unknown. In this study, a potential distribution of Skp2 in LSCC and its clinical implications was investigated by an immunohistochemical study. Overall, Skp2 overexpression was observed in 36.7% (37 of 102) patients and was significantly associated with lymph node metastasis (p=0.002) and was inversely associated with p27kip1 expression (p=0.026). Survival analysis using the Kaplan-Meier method showed that Skp2 overexpression was significantly associated with shorter disease-free and overall survival (p=0.0051 and p=0.0002, respectively). When Skp2 expression and p27kip1 expression were combined, patients with both Skp2 overexpression and reduced expression of p27kip1 revealed poorest disease-free and overall survival as compared to the other cases (p=0.0017 and p<0.0001, respectively). Additionally, in early stage (I, II) cases, Skp2 expression was also revealed to possess a significant prognostic factor in overall survival (p=0.0234), but not in disease-free survival (p=0.2055). By multivariate analysis using the Cox proportional hazards model, tumor grade, tumor size, clinical stage and Skp2 expression were independent prognostic factors both in disease-free and overall survival. These findings indicated that Skp2 expression was closely associated with tumor progression and represented an independent marker for prognosis of LSCC.     

Significance of Skp2 expression in human gastric carcinoma and the relationship between Skp2, p27 and PTEN expression

Objective： S-phase kinase-associated protein 2 （Skp2） is a positive regulator of G1-S transition and promotes ubiquitin-mediated proteolysis of the cyclin-dependent kinase inhibitor p27. Its overexpression has been implicated in cell transformation and oncogenesis. In this study, we investigated significance of Skp2 expression in human gastric carcinoma and the relationship between Skp2, p27 and PTEN expression. Methods： Immunohistochemical analysis was performed on 138 surgical resected primary gastric carcinoma specimens, 102 paired metastasis carcinoma tissue specimens in lymph node from the same set of 138 surgical resected primary gastric carcinoma specimens, 30 dysplasia specimens, 30 intestinal metaplasia specimens, and 20 normal gastric mucosa specimens for Skp2 and performed on the same set of 138 surgical resected primary gastric carcinoma specimens for p27 and PTEN. Results： Skp2 labeling frequency % was increased dramatically in intestinal metaplasia, dysplasia, and primary gastric carcinoma compared with normal gastric mucosa （P=0.000, all the same）. Skp2 labeling frequency % in metastasis gastric carcinoma in lymph node was significantly higher than primary gastric carcinoma （P=0.037）. Skp2 labeling frequency % was positively associated with differentiated degree （rho=0.315, P=0.000）, vessel invasion （rho=0.303, P=0.000） and lymph node metastasis （rho=0.254, P=0.000） respectively. An inverse correlation of Skp2 was observed with both its biochemical target p27 expression in gastric carcinoma （rho=-0.451, P=0.000） and with its putative negative regulator, the PTEN tumor suppressor protein （rho=-0.480, P=0.000）. p27 expression had positive relationship with PTEN expression in gastric carcinoma （rho=0.642, P=0.000）. Conclusion： Skp2 overexpression is correlated with carcinogenesis and progression of gastric carcinoma： elevated Skp2 expression is correlated with decreased p27 and PTEN in gastric carcinoma, and p27 expression is parallel with PTEN expression. These suggest that PTEN may regulate expression of p27 through the Skp2 pathway, and the effects of Skp2, p27 and PTEN together play an important role in carcinogenesis and progression of gastric carcinoma.     

Skp2与P27kip1在基底细胞癌及其临床病理特征中的表达

目的 检测S期激酶相关蛋白2(Skp2)与激酶抑制蛋白1(P27kip1)在基底细胞癌(BCC)中的表达,进而探明两者在BCC发生发展中的作用及其相关性,以及与临床病理特征的关系,并初步探讨Skp2与P27kip1在BCC 临床分型中的作用,尤其在硬化型中的作用.方法用免疫组织染色SP两步法检测50例BCC及30例正常...     

Skp2 protein expression in soft tissue sarcomas.

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 (SCF(skp2)). 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 studied in 182 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 (> or = 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.