HPV16基因整合与FHIT蛋白缺失在宫颈癌变中的作用

The integration of human papilloma viral 16 and its relationship with FHIT expression in cervical cancer

目的探讨HPV16的基因型整合状态及FHIT基因缺失在宫颈癌发生发展中的作用及相关性。方法选取44例宫颈癌、58例宫颈上皮内瘤样病变(CIN)和20例宫颈正常组织的患者,免疫组化检测宫颈FHIT蛋白的表达;并用多重PCR法检测HPV16 E2/E7表达。结果 122例单一HPV16阳性标本HPV16总整合率为78.69%,在正常宫颈组织、CIN1、CIN2、CIN3和宫颈癌中整合率分别为60.00%、66.67%、75.00%、86.96%和88.63%,随病变加重,整合率增强,组间差异有统计学意义(P<0.05);FHIT蛋白的总缺失率为43.44%,FHIT蛋白在正常宫颈组织、CIN1、CIN2、CIN3和宫颈癌中的缺失率分别为15.00%、20.00%、25.00%、43.48%和72.73%。FHIT蛋白的缺失率,随病变加重,缺失率增高,组间差异有统计学意义(P<0.05)。FHIT蛋白缺失在不同HPV16整合时不同,差异有统计学意义(P<0.05)。结论 HPV16基因整合和FHIT蛋白缺失在宫颈癌的发生、发展中起重要作用,HPV16基因整合可能通过诱导FHIT基因低表达从而促使宫颈癌发生发展。

Objective To explore the integration of human papilloma viral 16（HPV16） and its relationship with the expression of fragile histidine triad（FHIT） in cervical cancer. Methods The physical status of HPV16 E2/E7 was detected by Multiplex PCR（Polymerase chain reaction） in 44 patients with cervical cancer, 58 patients with CIN and 20 patients with normalcervix tissues. And immtmohistochemistry S-P assay was used to detect the ex- pression of FH/T before operation. Results The total integration rate of HPV16 was 78.69% in 122 cervical specimens with only HPV16 positive. The integration rates of HPV16 were 60.00%, 66.67%, 75.00%, 86.96% and 88.63%, in normal cervix tissues, CIN1,CIN2,CIN3 and cervical cancer. And it showed an increasing trend in different cervical lesions（X^2 =5.317 P=0.003〈0.05）; The total descending rate of FHIT was 43.44%, the descending rates of FHIT were 15.00%20.00%, 25.00%, 43.48% and 72.73%, respectively in different cervical lesions. The difference was statistically significant （X^2 =9.931 P=0.002 〈0.05）. The difference between the total integration of HPV16 and the total descending expression of FHIT was siginificant （X^2 = 11.211 P=0.002, Kruskal WaUis test）. Conclusion There is a close relationship between HPV16 genome integration correlates and the descending expression of FH1T in the progression of cervical lesion.