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目的研究端粒结合蛋白TRF1、TRF2在宫颈鳞癌发生发展中的作用并分析HPV16、HPV18感染与TRF1、TRF2蛋白表达的关系。方法随机选择南华大学附属第一医院病理科2005年9月至2006年10月期间的组织石蜡块标本共86例,采用原位杂交方法检测HPV16、HPV18在15例正常宫颈上皮、36例宫颈上皮内瘤变(CIN)和35例宫颈鳞癌组织中的感染情况;采用免疫组化方法检测所有组织标本中TRF1、TRF2蛋白的表达。结果(1)HPV16、HPV18阳性感染率CIN组[63.9%(23/36)]和宫颈鳞癌组[97.1%(34/35)]显著高于正常组[20.0%(3/15)](χ2=30.639,P<0.01)。(2)TRF1阳性表达率宫颈鳞癌组[40.0%(14/35)]显著低于CIN组[63.9%(23/36)]和正常组[86.7%(13/15)](χ2=10.237,P<0.01);CINⅢ组[42.9%(6/14)]显著低于CINⅠ组[90.0(9/10)](χ2=5.531,P<0.01)。TRF2阳性表达率宫颈鳞癌组[80.0%(28/35)]显著高于CIN组[52.8%(19/36)]和正常组[33.3%(5/15)](χ2=11.096,P<0.01)。(3)HPV16、HPV18感染与TRF1蛋白的表达强度负相关(Rs=-0.302,P<0.05),与TRF2蛋白的表达强度正相关(Rs=0.452,P<0.01)。结论TRF1、TRF2在宫颈鳞癌的发展中起重要作用。TRF1表达的下调和TRF2表达的上调与HPV16、HPV18感染致宫颈鳞癌密切相关。
Objective To study the role of telomere binding protein TRF1 and TRF2 in the development of cervical squamous cell carcinoma and to analyze the relationship between HPV16 and HPV18 infection and TRF1 and TRF2 protein expression. Methods Totally 86 cases of tissue paraffin blocks were collected from Department of Pathology, the First Affiliated Hospital of Nanhua University from September 2005 to October 2006. The in situ hybridization was used to detect the expression of HPV16 and HPV18 in 15 cases of normal cervical epithelium and 36 cases of cervical epithelium (CIN) and 35 cases of cervical squamous cell carcinoma. Immunohistochemistry was used to detect the expression of TRF1 and TRF2 in all tissues. Results The positive rates of HPV16 and HPV18 in CIN group (63.9% (23/36) and cervical squamous cell carcinoma group (97.1%, 34/35) were significantly higher than those in normal group [20.0% (3/15)] χ2 = 30.639, P <0.01). (2) The positive rate of TRF1 expression in cervical squamous cell carcinoma group (40.0%, 14/35) was significantly lower than that in CIN group (63.9%, 23/36) and that in normal group (86.7%, 13/15) , P <0.01). CINⅢ group [42.9% (6/14)] was significantly lower than CINⅠ group [90.0 (9/10)] (χ2 = 5.531, P <0.01). The positive expression rates of TRF2 in cervical squamous cell carcinoma group (80.0%, 28/35) were significantly higher than those in CIN group (52.8%, 19/36) and normal group (33.3%, 5/15) (χ2 = 11.096, P < 0.01). (3) There was a negative correlation between HPV16 and HPV18 infection and TRF1 protein expression (Rs = -0.302, P <0.05), and positive correlation with TRF2 protein expression (Rs = 0.452, P <0.01). Conclusion TRF1 and TRF2 play an important role in the development of cervical squamous cell carcinoma. Down-regulation of TRF1 expression and up-regulation of TRF2 expression are closely related to cervical squamous cell carcinoma of HPV16 and HPV18 infection.