【作者】 冯毅；

【导师】 吕智；

【作者基本信息】 山西医科大学 ， 骨科学， 2006， 硕士

【摘要】 目的:研究骨巨细胞瘤(Giant cell tumor of bone, GCT)中p73、p15蛋白的表达和DNA倍性与其生物学行为的相关性,探讨p73、p15蛋白表达、DNA倍性三者之间的联系和作用,以及p73、p15蛋白对细胞周期的影响,从而一方面确定p73、p15蛋白表达和DNA倍性在GCT预后评估中的作用,另一方面揭示p73和p15在GCT中的变化和作用机制。方法:实验选取山西医科大学第二医院病理科2000~2005年间经手术切除的GCT石蜡包埋组织30例。标本组按照Jaffe分级分为I级16例,II级8例,III级6例;按照Ennecking分期为1期6例,2期13例,3期11例;按照术后有无复发分为复发8例,无复发22例;按照有无转移分为转移4例,无转移26例。通过免疫组化检测标本组中的p15蛋白和p73蛋白的表达;通过流式细胞术检测标本组DNA的含量并拟合出细胞周期的分布。结果:p73蛋白和p15蛋白阳性表达主要位于GCT的细胞核,亦可同时见于胞浆,呈细颗粒状。p73蛋白和p15蛋白阳性表达均主要见于单核基质细胞;p73蛋白和p15蛋白在GCT中阳性表达率分别为40%(12/30)和56.7%(17/30); p73蛋白和p15蛋白在GCT中的表达与Ennecking分期存在相关性,二者的表达强度随Ennecking分期的增高而增加(P<0.05),二者在复发组的表达均高于无复发组(P<0.05,P<0.01),另外,p15蛋白的表达在转移组高于无转移组(P<0.01);标本组中DNA整倍体的为14例(46.7%),异倍体的为16例(53.3%),DNA倍性与Ennecking分期和是否复发存在相关性,异倍体在复发组高于无复发组(P<0.05),随Ennecking分期的增高而增加(P<0.01),但在有、无转移的两组间无差异(P>0.05);p73蛋白、p15蛋白的表达以及DNA倍性与Jaffe分级没有相关性(P>0.05);P73蛋白和p15蛋白表达在DNA异倍体组均高于整倍体组(P<0.05);p73、15蛋白阳性表达组G0/G1期细胞均低于阴性表达组(P<0.05,P<0.01),S期细胞均高于阴性表达组(P<0.05,P<0.01);经Sperman相关性检验p73、15蛋白在GCT中的表达呈正相关(P<0.05)。结论: p73、p15蛋白表达以及DNA倍性可以用来评估GCT的临床预后。无论是p73蛋白还是p15蛋白在GCT中均不能发挥其抑制细胞增殖的作用,二者在GCT中的表达的相关性可能是肿瘤抑制基因网络性结构复杂性的表现,并可能在肿瘤的发生、发展中起作用。更多还原

【Abstract】 Objective:This paper was designed to study the correlation of the expression of p73, p15 protein as well as DNA ploidy and the biology behavior of Giant cell tumor of bone (GCT), and the interaction among the p73 , p15 protein and DNA ploidy, and the effect that p73 and p15 bring to the cell cycle, thus on the one hand to determine the value of p73, p15 protein as well as DNA ploidy in prognosis for GCT, on the other hand to realized the diversification and action of p73 and p15 in GCT.Methods: We select 30 GCT paraffin samples which had been excised in surgery between 2000 and 2005 from the pathology department of the second hospital of Shanxi medical college. The specimen group divides into 16 cases of grade I, 8 cases of grade II , 6 cases of grade III as the Jaffe grading, and 6 cases of stage1 , 13 cases of stage 2, 11 cases of stage 3 as Ennecking’s stage; There were 8 cases recurred and 22 cases not recurred, 4 cases metastasized and 26 cases not metastasized. We detected the p73, p15 protein by using S-P immunohistochemistry and DNA ploidy by using flow cytometric DNA analysis.Results: p73 , p15 protein show itself the fine-grain shape are mainly located in the nucleus, also may be seen in the cytoblastema. Both of them expressed mainly in the mononuclear stroma cell. The positive expression rate of p73 protein and the p15 protein in the GCT samples are respectively 40% (12/30) and 56.7% (17/30); The expression of p73 and p15 protein correlate with Ennecking’s stage, the expression intensity increases along with the advances of Ennecking’s stage (P < 0.05), and is higher in the recured group than not recured group(P < 0.05, P < 0.01). In addition, the expression of p15 protein is higher in the metastasized group than not (P < 0.01). In specimen group, 14 samples(46.7%) is DNA euploid and 16 samples (53.3%) is DNA heteroploid. DNA ploidy correlate with the Ennecking’s stage and whether recurred. The heteroploid rate in recured group is higher than not recured (P < 0.05), and increases along with the advances of Ennecking’s stage (P < 0.01), but there is no discrepancy during the two groups that metastasized and not (P > 0.05); The expression of p73 , p15 protein as well as DNA ploidy does not correlate with the Jaffe’s grading (P > 0.05); The expression of P73, p15 protein is both higher in the heteroploid group than the euploid group (P < 0.05); The G0/G1 stage cells is lower in p73, p15 protein positive group than in the negative group (P < 0.05, P < 0.01), and the S stage cells is higher in the positive group(P < 0.05, P < 0.01); The expression of the p73 protein and p15 protein present the correlation after the Sperman relevance examination (P < 0.05).Conclusions: There is a statistically significant correlation between the expression of p73, p15更多还原