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目的:探讨TGF-β1及P53基因第72位密码子多态性与宫颈癌发生的关系。方法:对宫颈组织标本(包括39例宫颈鳞癌,17例宫颈上皮内瘤变(CIN)Ⅱ-Ⅲ级与17例CINⅠ级-正常宫颈)进行免疫组化法观察TGF-β1蛋白表达和用直接PCR法检测宫颈组织标本中P53 codon 72的基因型,分析其与宫颈癌发生发展之间的相关性。结果:TGF-β1的阳性率在CINⅠ组、CINⅡ-Ⅲ组分别为:11.8%、35.3%,而浸润癌组阳性率为64.3%,与前两者比较有显著性差异(P=0.0001)。TGF-β1表达与宫颈癌的临床分期有关(P=0.016),但与细胞分化程度及淋巴结转移与否无关(P=0.966;P=0.254)。在CIN样本中检出P53 codon 72 Arg/Arg、Arg/Pro及Pro/Pro基因型分别为52.9%、38.2%及5.9%;而宫颈鳞癌组织其中检出率分别为35.9%、46.2%及17.9%。Pro/Pro基因型在宫颈鳞癌组中所占比例显著高于CIN组(P=0.018,OR=3.300,95%CI=1.192-9.136),而Arg/Pro基因型与其比较,在两组间的分布无显著差异(P=0.205,OR=1.488,95%CI=0.804-2.756)。P53 codon 72 Pro/Pro基因型检测率在宫颈癌及CIN组织中,随着TGF-β1蛋白的表达增强,Pro/Pro检测率逐渐增高,两者呈正相关(r=0.444,P=0.006)。结论:TGF-β1的表达与宫颈鳞癌的发生发展有相关,Pro/Pro基因型是宫颈鳞癌的遗传易感性基因,与TGF-β1有协同作用。
Objective: To investigate the relationship between the codon 72 polymorphism of TGF-β1 and P53 gene and the occurrence of cervical cancer. Methods: The expression of TGF-β1 protein in cervical tissue samples (including 39 cases of cervical squamous cell carcinoma, 17 cases of cervical intraepithelial neoplasia (CIN) Ⅱ-Ⅲ and 17 cases of CINⅠ-normal cervical) was examined by immunohistochemistry The genotypes of P53 codon 72 in cervical tissue samples were detected by direct PCR, and the correlation between P53 codon 72 and the occurrence and development of cervical cancer was analyzed. Results: The positive rate of TGF-β1 in CINⅠgroup and CINⅡ-Ⅲ group was 11.8% and 35.3% respectively, while the positive rate of invasive carcinoma was 64.3%, which was significantly different from the former two groups (P = 0.0001). The expression of TGF-β1 was correlated with the clinical stage of cervical cancer (P = 0.016), but not with the degree of cell differentiation and lymph node metastasis (P = 0.966; P = 0.254). The P53 codon 72 Arg / Arg, Arg / Pro and Pro / Pro genotypes were detected in CIN samples, which were 52.9%, 38.2% and 5.9%, respectively. The detection rate of cervical squamous cell carcinoma was 35.9%, 46.2% 17.9%. Pro / Pro genotype in cervical squamous cell carcinoma group was significantly higher than CIN group (P = 0.018, OR = 3.300,95% CI = 1.192-9.136), while Arg / Pro genotype compared with the CIN group There was no significant difference in distribution (P = 0.205, OR = 1.488, 95% CI = 0.804-2.756). The detection rate of P53 codon 72 Pro / Pro genotypes in cervical cancer and CIN tissues was positively correlated with the increase of TGF-β1 protein expression and the detection rate of Pro / Pro (r = 0.444, P = 0.006). Conclusion: The expression of TGF-β1 is correlated with the occurrence and development of cervical squamous cell carcinoma. The Pro / Pro genotype is a genetic predisposition to cervical squamous cell carcinoma and has a synergistic effect with TGF-β1.