摘要
目的:探讨宫颈病变中TGF-β1的表达、HPV16E7型内变异与宫颈癌的关系。方法:对宫颈组织标本[39例宫颈鳞癌,34例宫颈上皮内瘤变(CIN)Ⅱ-Ⅲ级与64例CINⅠ级宫颈组织]进行免疫组化法观察TGF-β1蛋白表达,同时多重HPV16E7引物进行巢式PCR扩增,并选择阳性扩增的基因片段DNA进行纯化、测序,检测基因变异。结果:TGF-β1的阳性率在CINⅠ组、CINⅡ-Ⅲ组、浸润癌组中分别为:14.06%,41.18%,82.05%,其表达与宫颈病变的进展程度呈正相关(P<0.001,r=0.556)。在宫颈鳞癌临床分期各组别中,TGF-β1的阳性率在Ⅰa、Ⅰb、Ⅱa、Ⅱb组中依次增高(P=0.024)。检测到HPV16E7阳性样本共55例(CINⅠ组9例、CINⅡ-Ⅲ组14例和浸润癌组32例),其中原型15例。HPV16E7基因突变株最常见的为T846C变异株,该变异株在CINⅠ、CINⅡ-Ⅲ和鳞癌组中突变频率分别为66.67%、78.57%、81.25%,总检出率为78.18%。TGF-β1的表达在HPV16E7原型组和在HPV16E7A647G突变株组中无统计学差异(P=0.456)。结论:TGF-β1的表达与宫颈鳞癌的发生发展呈正相关,TGF-β1可能成为宫颈癌早期防治检测指标之一。HPV16E7A647G突变株较原型未通过改变TGF-β1介导的信号途径影响其致瘤性。
Objective. To investigate the prevalence of HPV16 E7 polymorphism and the expression of transforming growth factor beta 1 (TGF-β1) in cervical cancer and precursor lesions. Methods.A total of 39 patients with cervical squamous-cell carcinoma (SCC) and 34 patients with cervical intraepithelial neoplasia (CIN) Ⅱ-Ⅲ and 64 patients with CIN Ⅰ were obtained from women un- dergoing biopsy or surgery. TGF-β1 expression was examined by immunocytochemical staining.HPV16 E7 was assayed by polymerase chain reaction (PCR) and PCR-directed sequencing meth- od, and the variations of the HPV16 E7 gene were investigated. Results. The prevalence of TGF- β1 was 14.06% in the CIN I group and 41. 18% in the CIN Ⅱ-Ⅲ group and 82.05% in the SCC group. The level of TGF-β1 expression steadily increased by the damaged degree of cervical epithelium (P〈0. 001, r=0. 556). In the groups classified by FIGO clinical stage, the positive expression rate of TGF-β1 was increasing from stage Ⅰ a to Ⅱ b (P=0. 024). Fifty-five (CIN Ⅰ, n=9, CIN Ⅱ-Ⅲ, n=14; SCC, n=32) of the 137 samples contained HPV16 E7 DNA. The most frequently found variation was T846C (78. 18 %). No significant difference was found in the frequencies of TGF-β1 expression between A647G variation group and prototype sequences group (P= 0. 456). Conclusion: There was positive correlation between TGF-β1 expression and squamous carcinoma of the cervix. TGF-β1 possibly becomes a screening indicator for cervical cancer. It was not found that HPV16 E7 A647G variation plays a role in cervical carcinogenesis through TGF-β1 connected pathway.
出处
《武汉大学学报(医学版)》
CAS
北大核心
2014年第4期507-510,共4页
Medical Journal of Wuhan University