【作者】 杨晓东；

【导师】 冷维春；

【作者基本信息】 吉林大学 ， 妇产科学， 2005， 硕士

【摘要】 宫颈癌是最常见的妇科恶性肿瘤,其发病原因及机制至今尚未完全明了。近年来随着分子生物学技术的发展,以癌基因的激活、抑癌基因的失活以及其相关蛋白表达异常在发病机制方面的研究日益受到重视并取得很大的进展。近年来研究表明,恶性肿瘤是一类细胞周期性疾病,细胞周期调节失控与肿瘤的发生有密切的关系。细胞周期—细胞周期依赖性蛋白激酶—细胞周期依赖性蛋白激酶抑制因子组成的立体网络系统对细胞周期起重要的调控作用。p27是一个新近发现的细胞周期依赖性激酶抑制剂,为直接干预G₁/S期转换的负性调控因子,在细胞对于细胞外信号的反映调节中起关键作用。在肿瘤细胞中p27基因很少发生突变,在绝大多数肿瘤中没有发现特异性p27基因的变化,p27在肿瘤中大多是以蛋白水平或活性的改变而发挥作用。p27水平降低可能使肿瘤细胞对抗增殖信号失去敏感性,从而间接促进了肿瘤的发生和发展。p27可以通过干扰细胞增殖的速度和细胞凋亡的发生来影响肿瘤的发生、发展,而肿瘤的发生又与癌基因/抑癌基因的突变有着密切的关系。本文主要研究p27在宫颈鳞癌中的表达,探讨其在宫颈癌发生、发展过程中的变化及意义。目的:研究细胞周期相关蛋白p27在宫颈鳞状上皮细胞癌中的表达,探讨其在宫颈癌发生、发展过更多还原

【Abstract】 Cervical cancer is the most common malignant tumor in Gynecology, its etiology and mechanisms is not clarified. Recently, with the development of the Molecular Biochemicals, the research in oncogene activation, anti-oncogene inactivation and ectopic expression of its related proteins are reconstructed and make great progress. As a type of cell cycle diseases, tumor is closely correlated with regulation being out of control. Cycliln, cyclin-dependent kinase (CDK) and cyclin-dependent kinase inhibitor(CDKI) complexes play important roles in the controlling the cell cycle. P27 is cycl in-dependent kinase inhibitor that was detected newly and it is negative factor regulate cell cycle traverse during G1/S. It plays an important role in regulating of outside signal for cell. p27 genetic mutation is rarely in tumour cells. The level of p27 of protein decrease or its activity change in tumor. There is not specificity p27 gene mutation in most tumors. As the level of p27 decreasein tumor, tumor cell may lost sensitivity for anti-hyperplasy signal. Thus promote tumor cell occurrence and development indirectly. p27 intervene cell hyperplasy rate and cell apoptosis occurrence, so it can effect tumor development, tumor development is close relation with oncogene and anti-oncogene mutation. This article mainly study the expression of p27 in cervical squamous carcinoma and investigate its variation and significance in cervical cancers generation and development. Objective: To study the expression of the cyclin-dependent kinase inhibitor p27 protein in cervical squamous cell carcinoma and discuss its significance. Methods: The expression of p27 were detected with the immunohistochemical stain in 21 cases of normal cervical squamous epithelium, 20 cases cervical intraepithelial neoplasia (CIN) and 52 cases cervical invasive squamous cell carcinoma , including FIGOI 12 cases, FIGOII 20 cases, FIGOIII 16 cases and FIGOIV 4 cases. Meanwhile , pathologic grade of cervical carcinoma include 26 poorly differentiation cases , 14 moderately differentiation cases and 12 well differentiation cases. Result: ①Thestrong positive expression of p27 in normal cevix is 19/21, postive expression of p27 is 2/21, positive expression rate is 100%, and its positive expression in CIN is 60%, that in cervical carcinoma is 34. 62%. With the development of the cervix disease, the expression rates of p27 was gradually decreased in the normal cervical tissues, CIN tissues and invasive cervical carcinomas. The difference was significant (p<0.05). ② In invasive cervical carcinoma, the positive expression rate of p27 in well differentiation is 83. 33%, that in moderately expression is 42. 86% and 7. 69% in poorly differention. The difference of expression rates of p27 was significant in the poorly differentiation, moderately differentiation and well. differentiation(x2=21.33, P<0.005). The expression had negative correlation with the pathologic grade (rs=-0. 797, P<0.001). ③The positive expression rates of p27 has significant differences between the cervical cancer with lymphatic metastasis and without lymphatic metastasis (p<0. 05). (4) In invasive cervical carcinoma , the positive expression of p27 in stage Ⅰ is 75%, that in stage Ⅱ is 35%, that in stage Ⅲ and Ⅳ is 10%, strong immunostaining更多还原