FHIT基因微卫星变异及人乳头瘤病毒感染与宫颈癌关系的研究

Study on relationship between microsatellite alterations of FHIT gene and HPV infection and cervical carcinoma

目的:探讨脆性组氨酸三联体(FHIT)基因微卫星变异及人乳头瘤病毒感染与宫颈癌的关系。方法:选取FHIT基因的两个微卫星多态标记,采用聚合酶链反应(PCR)法对50例宫颈癌及40例宫颈上皮内瘤样病变(CIN)组织进行杂合性丢失(LOH)、微卫星不稳定性(MI)及HPV16感染的检测。结果:在D3S1234位点上宫颈癌和CIN的LOH发生率分别为46%(23/50)和40%(16/40),差异无统计学意义,P=0.361;宫颈癌和CIN的MI发生率分别为18%(9/50)和12.5%(5/40),差异无统计学意义,P=0.339。在D3S4103位点上宫颈癌和CIN的LOH发生率分别为40%(20/50)和37.5%(15/40),差异无统计学意义,P=0.491;宫颈癌和CIN的MI发生率分别为14%(7/50)和7.5%(3/40),差异无统计学意义,P=0.265。但宫颈癌在两位点上LOH和MI发生频率均高于CIN且高级别CIN发生率高于低级别CIN。在50例宫颈癌组织中HPV16感染阳性组的LOH和MI发生率分别为79.5%(35/44)和31.8%(14/44),阴性组LOH发生2例,MI发生1例,两组间LOH的差异有统计学意义,P=0.003,MI的差异无统计学意义,P=0.645。在40例CIN中HPV16感染阳性组的LOH和MI发生率分别为82.4%(14/17)和35.3%(6/17),在HPV16感染阴性组中LOH和MI的发生率分别为52.2%(12/23)和17.4(4/23);LOH的差异有统计学意义,P=0.048,MI的差异无统计学意义,P=0.274。结论:FHIT基因的变异可能发生在宫颈癌变的晚期。

OBJECTIVE： To explore the relationship between microsatellite alterations of FHIT gene and HPV infection and the development of cervical carcinoma. METHODS：Two sites of microsatellite polymorphism of FHIT gene were selected, and LOH and MI were detected with polymerase chain reaction （PCR） technique in 50 cases of cervical carcinoma and 40 cases of cervical intraepithelial neoplasia （CIN）, and the infection state of HPV16 was also detec- ted. RESULTS.. At D3S1234, the LOH rate of cervical carcinomas and CINs were 46% （23/50） and 40% （16/40） separately. There was no significant difference between cervical carcinomas and CINs, P=0. 361. The MI rate of cervical carcinomas and CINs were 18%（9/50） and 12.5% （5/40） separately. There was no significant difference between cervical carcinomas and CINs, P = 0. 339. At D3S4103, the LOH rate of cervical carcinomas and CINs were 400/00 （20/50） and 37.50/00 （15/40） separately. There was no significant difference between cervical carcinomas and CINs, P= 0. 491. The MI rate of cervical carcinomas and CINs were 14 % （7/50） and 7.5 0%（3/40） separately. There was no significant difference between cervical carcinomas and CINs, P= 0. 265. The rates of LOH and MI for cervical carcinomas were higher than those for CIN. In 50 cervical carcinomas, the positive rates of LOH for HPV16 infenction were 79.5 % （35/44）, and MI were 31.8 % （14/44） ;the negative rate of LOH was 33.3%（2/6）, MI 16.7%（1/6）, and there was a significant difference between HPV16 （ ＋） and HPV16 （ - ） in respect to their positive rate of LOH, P= 0. 003, no significant difference of MI, P=0. 645. In 40 CINs, the positive rate of LOH for HPV16 infenction was 82.4% （ 14/17 ）, MI 35.3% （ 6/17 ） ; the negative rate of LOH was 52.2 % （12/23）, MI 17.4 （4/23）, and there was a significant difference between HPV16 （＋） and HPV16 （ - ） in respect to their positive rate of LOH, P=0. 048, no significant difference of MI, P=0. 274. CONCLUSION： The FHIT gene change is a relatively late event in cervical carcinomas.