宫颈癌组织中MCM4、TFF2的表达及其与HPV_(16/18)感染的相关性研究

研究MCM4、TFF2在宫颈癌组织中的表达及其与HPV16/18感染的相关性,以探讨宫颈癌的发生机制,进一步寻找有利于宫颈癌诊断的新的分子标志物,以指导其诊断与预后。采用免疫组织化学方法对50例宫颈癌石蜡标本、宫颈上皮内瘤变CINⅠ20例、CINⅡ-Ⅲ20例、正常宫颈组织20例进行MCM4、TFF2的检测,同时采用PCR技术检测HPV16/18感染情况。结果:(1)在宫颈癌组织中MCM4的阳性率高于CIN和正常宫颈组织,差异有统计学意义(P<0.05),且MCM4阳性表达率与病理分级、淋巴结转移有关,差异有统计学意义(均P<0.05)。在宫颈癌组织中MCM4的阳性表达率与年龄分组、临床分期无关(均P>0.05)。在宫颈癌组织中TFF2的阳性率低于CIN和正常宫颈组织,差异有统计学意义(P<0.05),且TFF2阳性表达率与年龄分组有关,差异有统计学意义(P<0.05),其阳性表达率均与临床分期、病理分级、淋巴转移无关(均P>0.05);(2)HPV16/18在正常宫颈组织、CIN和宫颈癌中的阳性率逐渐升高,差异有统计学意义(P<0.05),但与年龄、临床分期、病理分级、淋巴转移无关(均P>0.05);(3)在宫颈癌组织中,MCM4与HPV16/18感染呈正相关(rs=0.634,P<0.01),TFF2与MCM4、HPV16/18感染呈负相关(rs=-0.375,P<0.01;rs=-0.500,P<0.01)。宫颈上皮内瘤变及宫颈癌组织中MCM4、TFF2表达的改变可能与HPV16/18感染有关,且互相作用,共同影响CIN的发展及宫颈癌的发生。这些指标综合分析可能为阐明HPV16/18的恶性转化机制以及为提高宫颈癌及其癌前病变诊断率提供参考依据。MCM4的异常表达与宫颈癌的恶变程度有关,可作为宫颈癌筛查、预后判断的有利指标。

Expressions of the minichromosome maintenance protein-4 and trefoil factor-2 in uterine cervical cancer tissues and their correlation with HPV16/18 infection

To investigate the correlation between the expression of the minichromosome maintenance protein-4(MCM4) and trefoil factor-2(TFF2) in uterine cervical cancer tissues and the infection with HPV16/18,in order to explore the mechanism of carcinogenesis,formalin-fixed,paraffin-embedded samples including 50 cases with squamaous cell carcinoma,each of 20 cases of cervical intraepithelial neoplasm of CINI and CINII-III and 20 normal cervical tissues were collected and subjected to detect the expressions of MCM4 and TFF2 in these tissues.Meanwhile,the condition of infection with HPV16-18 was analyzed by PCR assay.The results showed that:(1) There were significant differences in the positive rate of MCM4 between uterine cancerous tissues and normal cervical tissues and it was higher in the former(P<0.05).The expression rate of MCM-4 was closely related to the tumor grades and lymph node metastasis(P<0.05),yet,it did not show any relationship with age or clinical stages(P>0.05).However,the expression rate of TFF-2 in the uterine cancerous tissues was lower than those of CIN and normal cervical tissues with significant difference(P<0.05) and related to age(P<0.05),but it showed no relationship with clinical stages,tumor grades and lymph node metastasis(P>0.05).(2) The positive rate of HPV16-18 infection showed significant differences between cervical carcinoma CIN and normal tissues(P<0.05),but it had no any relationship to tumor grades,clinical stages,age and lymph node metastasis(P>0.05).(3) In the uterine cervical tissues,positive correlation existed between the expression of MCM4 and the HPV16-18 infection(rs=0.634,P<0,01)but negative correlations between TFF2 /MCM4 and TFF2/HPV16-18 were demonstrated(rs= 0.375,P<0.01;rs=0.500,P<0.01)respectively.From these observations,it is evident that the changes in the expressions of MCM-4 and TFF-2 in uterine cervical epithelium may be associated with the HPV16-18 infection and they may interact or influence each other,thus relating to the progression of CIN and carcinogenesis of cervical carcinoma.