KI-67在儿童膀胱横纹肌肉瘤中的表达及其临床意义

发布时间：2018-05-19 12:14

本文选题：KI-67 + 膀胱横纹肌肉瘤　；参考：《南方医科大学》2017年硕士论文

【摘要】：目的及背景:横纹肌肉瘤(RMS)是最常见的软组织肿瘤,在儿童和青少年肿瘤中占5%。在美国20岁以下的患者中,每年估计有350例新病例诊断RMS。相比之下,RMS是非常罕见于成人的,其有轻微的男性优势(男性发病人数是女性的1.4倍),但是统计学上没有发病率的显着差异。横纹肌肉瘤可以发生在身体的任何部位,但是横纹肌肉瘤的发生机制及遗传机制直至目前仍不甚了解。有文章总结了最近的全基因组研究,认识到PAX-FKHR基因融合状态在RMS中的预后价值,其中甚至牵连了肿瘤的逃避抑制机制,但仍不能提出能够应用的诊断和预后生物标志物,以应对个体靶向治疗和显着改善横纹肌肉瘤的预后。因此寻找、发现一个能够方便准备预测横纹肌肉瘤患者生存的因素(如病理分期系统、临床分期系统、分子生物标记物)迫在眉睫。Ki-67蛋白是可识别的细胞周期中的核抗原,与细胞增殖密切相关。在泌尿系肿瘤中,大多数文献认为Ki-67蛋白在泌尿系肿瘤中的表达与肿瘤分级、TNM分期、术后复发、转移和预后高度相关,尤其是在其术后预后方面的作用。但关于KI-67在横纹肌肉瘤中的研究现在还非常稀少,因此本研究采用免疫组化的方法检测横纹肌肉瘤组织中Ki-67蛋白的表达,探讨Ki-67和横纹肌肉瘤患者预后之间的关系。方法:收集南方医科大学珠江医院2010年1月份至2016年1月份的26例儿童(14岁以下)膀胱横纹肌肉瘤组织。其中男性23人,女性3人;年龄从1岁至9岁,平均年龄为3.7±1.5岁。采用免疫组化S-P法检测这些肿瘤标本的KI-67蛋白的表达,并采用常用的统计学分析软件IMB SPSS 20.0软件进行统计学分析,在KI-67蛋白表达与患者年龄、肿瘤大小(cm)的分析中采用两样本独立T检验,KI-67蛋白的表达与性别、肌层侵犯、切缘阳性、肿瘤数目中采用卡方分析,采用秩和检验分析KI-67蛋白的表达与横纹肌肉瘤Stage分期。临床分组和危险分层的相关性。采用Kaplan-Meier方法分析KI-67蛋白表达与儿童横纹肌肉瘤术后预后关系。最后还初步探索KI-67蛋白的表达在儿童横纹肌肉瘤的化疗前后的变化。结果:研究发现KI-67在儿童横纹肌肉瘤的表达与患者的性别、年龄无相关,但在病理组织学特征方面,我们发现KI-67蛋白表达与肿瘤大小、切缘阳性、肌层侵犯、肿瘤数目未显示出显著的相关性,但其KI-67蛋白的表达与是否出现淋巴结转移是强相关(p=0.033,0.05P0.01),没有发现KI-67蛋白在儿童横纹肌肉瘤中的表达与Stage分期、临床分组、危险分层之间的相关性,经Kaplan-meier法进行预后分析,我们仍然可以看到KI-67高表达组与KI-67低表达之间在生存预后方面有明显的统计学差异(P=0.0108,P0.05),KI-67低表达组患者比Ki-67高表达组患者拥有更好的预后。结论:在儿童膀胱横纹肌肉瘤患者中,KI-67低表达组患者比Ki-67高表达组患者拥有更好的预后,可以说KI-67蛋白的表达是儿童膀胱横纹肌肉瘤术后的预后因素。
[Abstract]:Objective and background: rhabdomyosarcoma (RMS) is the most common soft tissue tumor in children and adolescents. An estimated 350 new cases of RMS are diagnosed annually in patients under the age of 20 in the United States. By contrast RMS is very rare in adults and has a slight male predominance (the number of male cases is 1.4 times higher than that of females but there is no statistically significant difference in the incidence of RMS). Rhabdomyosarcoma can occur in any part of the body, but the pathogenesis and genetic mechanism of rhabdomyosarcoma are still unknown. Some articles have summarized the recent genome studies and recognized the prognostic value of PAX-FKHR gene fusion status in RMS, which even implicated in the mechanism of tumor escape inhibition, but it is still unable to propose diagnostic and prognostic biomarkers that can be applied. In order to deal with individual targeted therapy and significantly improve the prognosis of rhabdomyosarcoma. Therefore, to find a factor (such as pathological staging system, clinical staging system, molecular biomarker) that can be easily prepared to predict the survival of rhabdomyosarcoma patients, the Ki-67 protein is identified as the nuclear antigen in the cell cycle. It is closely related to cell proliferation. In urological tumors, the expression of Ki-67 protein in urological tumors is highly correlated with tumor grade, recurrence, metastasis and prognosis, especially in postoperative prognosis. However, the study of KI-67 in rhabdomyosarcoma is still very rare, so the expression of Ki-67 protein in rhabdomyosarcoma was detected by immunohistochemical method to explore the relationship between Ki-67 and prognosis of rhabdomyosarcoma. Methods: 26 cases of bladder rhabdomyosarcoma from January 2010 to January 2016 in Zhujiang Hospital of Southern Medical University were collected. There were 23 males and 3 females, aged from 1 to 9 years, with an average age of 3.7 卤1.5 years. Immunohistochemical S-P method was used to detect the expression of KI-67 protein in these tumor specimens, and IMB SPSS 20.0 software was used to analyze the expression of KI-67 protein with the age of the patients. The expression and sex of KI-67 protein, invasion of muscle layer, positive margin of tumor, chi-square analysis and rank sum test were used to analyze the expression of KI-67 protein and Stage stage of rhabdomyosarcoma. Correlation between clinical grouping and risk stratification. Kaplan-Meier method was used to analyze the relationship between the expression of KI-67 protein and postoperative prognosis of children with rhabdomyoma. Finally, the expression of KI-67 protein before and after chemotherapy in children rhabdomyosarcoma was preliminarily investigated. Results: the expression of KI-67 in rhabdomyosarcoma of children was not correlated with sex and age, but in histopathological features, we found that the expression of KI-67 protein was correlated with tumor size, incisal margin positive, and invasion of muscle layer. There was no significant correlation between the number of tumors, but the expression of KI-67 protein was strongly correlated with lymph node metastasis. There was no significant correlation between the expression of KI-67 protein and Stage stage and clinical grouping in children rhabdomyosarcoma. The correlation between risk stratification was analyzed by Kaplan-meier method. We can still see that there is a significant difference in survival and prognosis between the high expression group of KI-67 and the low expression of KI-67. The patients with low expression of P0. 0108 and P0. 05 + KI-67 have better prognosis than those with high expression of Ki-67. Conclusion: in children with bladder rhabdomyosarcoma, the patients with low expression of KI-67 have better prognosis than those with high expression of Ki-67. It can be said that the expression of KI-67 protein is a prognostic factor in children with bladder rhabdomyosarcoma after operation.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.14

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