低氧诱导因子-1α和p53蛋白在宫颈癌中的表达

Expressions of HIF-1α and p53 in cervical carcinoma and intraepithelial neoplasia

目的探讨低氧诱导因子-1α和p53蛋白在宫颈癌、宫颈上皮内瘤样变及正常宫颈组织中的表达及意义。方法采用免疫组化SP法检测低氧诱导因子-1α和p53蛋白在54例宫颈癌、28例宫颈上皮内瘤样变和20例正常宫颈组织中的表达情况。结果①低氧诱导因子-1α和p53蛋白在宫颈癌中强阳性表达、宫颈上皮内瘤样变中少量表达、正常宫颈组织中无表达,三者之间有显著性差异(2χ=25.974,P<0.01);②低氧诱导因子-1α在宫颈上皮内瘤样变Ⅰ、Ⅱ、Ⅲ中阳性表达呈上升趋势,但无显著性差异(2χ=1.179,P>0.05),p53蛋白在宫颈上皮内瘤样变Ⅰ、Ⅱ、Ⅲ中表达无显著性差异(2χ=1.426,P>0.05);③低氧诱导因子-1α表达与宫颈癌临床分期显著相关(2χ=7.488,P<0.05),与分化程度显著相关(2χ=8.589,P<0.05),与淋巴结转移显著相关(2χ=12.295,P<0.05),并且与肿瘤恶性程度成正相关(r=0.370,P<0.05),p53蛋白表达与宫颈癌临床分期显著相关(2χ=6.888,P<0.05);④低氧诱导因子-1α与p53蛋白在宫颈癌组织中阳性表达呈正相关(r=0.339,P<0.01)。结论低氧诱导因子-1α和p53蛋白过度表达,在宫颈癌的发生、发展过程中具有重要作用,是宫颈癌发生的早期事件,其表达水平随着宫颈癌恶性程度的增加而增加,且低氧诱导因子-1α与宫颈癌的发展和转移有关;突变型p53蛋白表达增加的同时低氧诱导因子-1α表达增加,二者具有正相关性,联合检测可作为判定肿瘤恶性程度、预测转移和评估预后的指标。

Objective To investigate expressions and significances of hypoxia inducible factor-1 alpha （HIF-α） and p53 protein in cervical carcinoma, cervical intraepithelial neoplasia（CIN） and normal cervical tissues. Methods The expressions of HIF-α and p53 protein in 54 cases of cervical carcinoma, 28 cases of CIN, 20 cases of normal cervical tissues were detected with SP method of immuohistochemistry. Results ①HIF-α and p53 protein were strongly and positively expressed in cervical carcinoma, were slightly expressed in CIN and were not expressed in normal cervical tissues, and there were significant differences among the three groups （X^2 = 25. 974, all P 〈0. 01 ） ; ② The positive expressions of HIF-α in CIN I , CIN l/ and CINlll were increased gradually in order, but there were not any significant differences between them （X^2 = 1. 179, all P 〉 0. 05）, while in positive expressions of p53 protein in CIN I, CIN l/and CINlil,there were not any significant difference between them （X^2 = 1. 426, all P 〉0.05） ; ③ The expression of HIF-α was significantly correlated with clinical stage of cervical carcinoma （X^2 = 7. 488, P 〈 0. 05）, differentiation degree of tumor cells （X^2 = 8. 589, P 〈 0. 05） and lymphatic metastasis （X^2 = 12.295, P 〈 0. 05 ）, and it positively correlated with malignancy of the tumor （ r = 0. 370, P 〈 0. 05）. The expression of p53 protein was associated with clinical stage of cervical carcinoma （X^2 = 6.888, P 〈 0. 05） ; ④ The expression of HIF-α was correlated positively with that of p53 protein （r = 0. 339, P 〈 0. 01 ）. Conclusion Over-expressions of HIF-α and p53 protein in cervical carcinoma may play important roles in occurrence and development of cervical carcinoma. They are early event of development of cervical carcinoma and their levels of expression are increased as increase in malignancy of cervical carcinoma. While HIF- 1α is associated with development and metastasis of cervical carcinoma. When expression of mutative p53 protein increases, the expression of HIF-α is increased simultaneously, and there was a positive mutual relationship. Combined detection of expressions of HIF-α and p53 protein can be regarded as a index to iudex maliznancv of the tumor, oredict metastasis and evaluate proanosis of cervical carcinoma.