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Skp2、p27及E2F-1在骨巨细胞瘤中的表达及意义
The Expression and Significance of Skp2、p27 and E2F-1 in Giant Cell Tumor of Bone
【作者】 李翀;
【导师】 冯一中;
【作者基本信息】 苏州大学 , 病理学, 2009, 硕士
【摘要】 目的:研究骨巨细胞瘤中Skp2、p27及E2F-1的表达并探讨其与放射学分期、肿瘤复发及病理分级等的关系,为骨巨细胞瘤的生物学行为和预后判断提供依据。方法:运用免疫组织化学S-P法检测44例骨巨细胞瘤中Skp2、p27及E2F-1的表达情况,并分析其与放射学分期、肿瘤复发及病理分级等的关系。结果:(1)44例骨巨细胞瘤中,Skp2的阳性表达率为65.91%(29/44),随影像学分期(分为1型,2型,3型)的升高,Skp2的阳性率依次增高,分别为50%(10/20)、64.29%(9/14)及100%(10/10),差异有显著性统计学意义(P<0.05)。Skp2在复发组与未复发组的阳性表达率分别为91.67%(11/12)、56.25%(18/32),差异有显著性统计学意义(P<0.05)。(2)44例骨巨细胞瘤中,p27的阳性表达率为38.64%(17/44),随影像学分期(分为1型,2型,3型)的升高,p27阳性率依次降低,分别为60%(12/20),28.57%(4/14)及10%(1/10),差异有显著性统计学意义(P<0.05),其中1型与3型相比差异均有显著性统计学意义(P<0.05)。p27在复发组与未复发组的阳性表达率分别为8.33%(1/12)、50%(16/32),差异有显著性统计学意义(P<0.05)。(3)44例骨巨细胞瘤中,E2F-1的阳性表达率为63.64%(28/44),随影像学分期(分为1型,2型,3型),E2F-1的阳性率分别为50%(10/20),71.43%(10/14)及80%(8/10),但差异无统计学意义(P>0.05)。E2F-1在复发组与未复发组的阳性表达率分别为75.00%(9/12)、59.38%(19/32),差异无统计学意义(P>0.05)。(4)多因素Cox回归分析显示,骨皮质破坏或软组织浸润、手术方式、Skp2以及p27对复发均有明显影响,其中Skp2(RR=6.272)的阳性表达、骨皮质及软组织破坏(RR=0.170)是影响骨巨细胞瘤复发的危险因素,而p27(RR=0.214)阳性表达、截骨(RR=0.413)的手术方式则是骨巨细胞瘤复发的保护因素。(5)在本研究中,Skp2与p27的表达呈负相关(Spearman相关分析:P<0.05);Skp2与E2F-1的表达无相关关系(Spearman相关分析:P>0.05);p27与E2F-1的表达无相关性(Spearman相关分析P>0.05)。结论:在骨巨细胞瘤中,Skp2的阳性表达随着影像学分期的升高而升高,D27的阳性表达随着影像学分期的升高而降低,二者均与骨巨细胞瘤的复发有关,但二者的表达均与病理学分级无关,表明Skp2与p27在骨巨细胞瘤细胞的增殖过程中可能起重要作用,提示二者可作为骨巨细胞瘤预后的参考指标。E2F-1的阳性率亦随影像学分期的升高而升高,但无统计学意义。本研究同时表明,Skp2与p27的表达呈负相关,而Skp2与E2F-1、p27与E2F-1则无明确相关性,提示联合检测Skp2与p27可能可作为骨巨细胞瘤侵袭状态、复发倾向的判定以及手术治疗方式选择的一种参考指标。
【Abstract】 Objective:To study the expression of Skp2、p27 and E2F-1 protein in giant cell tumor of bone(GCT) and detect the correlation between their expression and radiological stage,tumor recurrence,pathological stage.Methods:Immunohistochemical SP staining method was used to detect the expression of Skp2、p27 and E2F-1 in 44 cases of GCT.And we analyze the relationship between these factors and radiological stage,tumor recurrence,pathological stage.Results:(1) The positive rate of Skp2 in 44 cases of GCT was 65.91%(29/44). According to radiological stage(stage 1,2 and 3),the positive rate of Skp2 was 50% (10/20) in stagel lower than 64.29%(9/14) in stage 2(P<0.05) and 100%(10/10) in stage 3(P<0.05).The positive rate of Skp2 in recurrent cases was 91.67%(11/12) higher than 56.25%(18/32) cases without recurrence(P<0.05).(2) The positive rate of p27 in 44 cases of GCT was 38.64%(17/44).According to radiological stage (stage 1,2 and 3),the positive rate of p27 in stage 1 was 60%(12/20) higher than 28.57%(4/14) in stage 2 and 10%(1/10) in stage 3(P<0.05).The positive rate of p27 in recurrent cases was 8.33%(1/12) lower than 50%(16/32) in cases without recurrence(P<0.05).(3) The positive rate of E2F-1 in 44 cases of GCT was 65.91% (29/44).According to radiological stage(stage 1,2 and 3),the positive rate of E2F-1 was 50%(10/20),71.43%(10/14) and 80%(8/10) in stage 1,stage 2 and stage 3, respectively.The positive rate of E2F-1 in every group had no significant defference. The positive rate of E2F-1 was 75.00%(9/12) and 59.38%(19/32) in recurrent cases and cases without recurrence,respectively(P>0.05).(4) Multiple factorial Cox regression analysis indicated that destruction of bony cortex or infiltration of parenchyma,operation modality,the positive rates of Skp2 and p27 had influence on recurrence of GCT.The positive rate of Skp2(RR=6.272) and destruction of bony cortex or infiltration of parenchyma(RR=0.170) were risk factors of recurrence of GCT.The positive rate of p27(RR=0.214),general and complete ectomy(RR=0.413) were protective factors of GCT.(5) In this study,Spearman correlation showed that there was a significant negative correlation between Skp2 and p27(P<0.05),no correlation between Skp2 and E2F-1(P>0.05),p27 and E2F-1(P>0.05).Conclusions:The positive rates of Skp2 are increased and The positive rates of p27 are decreased by the radiological stage of GCT.The two factors are both associated with recurrence of GCT and not associated with pathological stage of GCT.The results suggest that the two factors are concerned with the development and progression of GCT,and it indicate the factors may be regarded as one of valuable indexes of prognosis of GCT.The positive rates of E2F-1 have no significant difference in the radiological stage of GCT.And the study shows that there was a significant negative correlation between Skp2 and p27,no correlation between Skp2 and E2F-1,p27 and E2F-1.The result suggests that the combined detection of Skp2 and p27 may be regarded as one of valuable indexes of infiltrated state,decision of tendency to recur and selection of operation modality.
【Key words】 Giant cell tumor of bone; Skp2; p27; E2F-1; Immunohistochemistry;