FHIT在宫颈癌及宫颈上皮内瘤变的表达及意义

目的:探讨在宫颈癌和宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)发生中脆性组氨酸三联体(fragile histid ine triad,FHIT)基因表达异常的作用及与HPV感染的关系。方法:用免疫组化法检测67例宫颈癌、42例CINⅢ和35例正常宫颈上皮组织的FHIT的表达。用PCR法检测宫颈癌石蜡组织中的HPV DNA,并用直接测序法或反向核酸杂交法对HPV分型。结果:正常宫颈组织中FHIT基因表达下调率为8.6%,CINⅢ组为28.57%,宫颈癌组为46.27%,差异均有统计学意义(P<0.05)。CINⅢ组FHIT蛋白表达下调率虽比宫颈癌组为低,但组间无统计学差异(P=0.66)。67例宫颈癌病例中,高危型HPV感染阳性者的FHIT表达下降或缺失占55.32%,明显高于无高危型HPV感染者(20%)(P<0.05)。宫颈癌患者的年龄、临床分期、肿瘤组织学分级、肿瘤浸润深度和淋巴结转移与FHIT蛋白表达均无明显相关(P>0.05)。FHIT表达下调或缺失31例宫颈癌患者的5年生存率为77.1%,FHIT正常表达36例的5年生存率为79.3%(P>0.05)。结论:FHIT在宫颈癌及CINⅢ中的表达明显下调,可能与HPV感染协同在宫颈癌的发生中起了重要作用。而FHIT在宫颈癌发展中的作用及与预后的关系,有待大样本的进一步研究。

Expression and role of FHIT in the development of cervical intraepithelial neoplasia grade Ⅲ and cervical cancer

Objective:To investigate the potential association between the expression of FHIT protein and HPV infection in cervical cancer,and the role of FHIT in the development of cervical intraepithelial neoplasia grade Ⅲ (CINⅢ) and cervical cancer.Methods:FHIT protein expression was detected in 35 normal epithelium of cervix,42 CINⅢ and 67 cervical cancer cases.Detections were performed by rabbit antibody to human FHIT gene protein with citrate-microwave-sp immunohistochemical methods.HPV DNAs in 67 cervical cancer specimens were detected by polymerase chain reaction.HPV types were determined by either sequencing or reverse hybridization.Results:Reduced FHIT protein expression was observed in 8.6% normal epithelium,which was lower than 28.57% in CINⅢ(P<0.05) or 46.27% in cervical cancer cases(P<0.05).There is no significant difference(P>0.05) between the FHIT aberrant expression rate in CINⅢ and cervical cancer cases.The depressed expression rate of FHIT is significant higher in HPV DNA positive group 55.32% than that in HPV DNA negative cervical cancer cases 20%(P<0.05).None of the clinical stage or clinical pathologic prognostic parameters such as tumor differentiation and lymph metastasis showed a correlation with FHIT expression.The five years survival has no significant difference between FHIT normal expression cases(79.3%) and depressed expression cases(77.1%) in cervical cancer.Conclusions:The reduction of FHIT expression in CINⅢ and invasive cervical carcinoma may play a role in the development of cervical cancer associated with HPV infection.The further investigation is to be needed.