脆性组氨酸三联体基因在宫颈癌前病变和宫颈癌中的表达及其与p53和HPV16/18的关系

Expression of FHIT genes in CIN and cervical carcinoma and the relationship between FHIT gene and p53 and HPV16/18

目的探讨脆性组氨酸三联体(FHIT)基因缺失与p53的过度表达和人乳头状瘤病毒16和(或)18(HPV16/18)感染在宫颈癌前病变(CIN)和宫颈癌(CC)发生发展中的作用和意义。方法采用免疫组化SP法检测52例CIN和69例CC中的FHIT基因和p53的表达,以原位杂交方法检测HPV16/18感染情况,并以18例正常宫颈组织作为对照。结果FHIT在正常宫颈组织(正常组)中呈阳性表达；FHIT在宫颈CIN组中的阴性率为30．8%,在CINⅢ期的表达,明显高于正常组和CINⅠ、Ⅱ期(P＜0．01)；在CC组中阴性率为66．7%(46/69),明显高于正常组和CIN组(P＜0．01),且随细胞分化的降低,FHIT阴性率上升。p53和HPV16/18在CC组的阳性率分别达56．5%(39/69)和84．1%(58/69),均高于CIN和正常组(P＜0．05),且CC组的p53阳性率随细胞分化的降低而升高(P＜0．01)。CIN和CC组的FHIT阳性和阴性者,p53阳性率差异均无统计学意义(P＞0．05),相关性分析也显示无相关关系；但两组FHIT阴性者的HPV16/18感染率明显高于FHIT正常表达者(P＜0．01),FHIT与HPV呈负相关关系。结论FHIT基因缺失与宫颈癌发生有关,它在CIN中的缺失可能可作为高危型CIN人群的筛选和宫颈癌早期诊断指标。CIN和CC中的FHIT缺失常与p53过度表达同时存在,但两者间无相关性。HPV16/18可能是引起FHIT和p53异常的共同原因。

Objective To investigate the role and significance of FHIT genes depletion, p53 overexpression and HPV16/18 infection in cervical intraepithelial neoplasia （CIN） and cervical carcinoma （CC）. Methods Tumor samples taken from 52 cases of CIN and 69 cases of CC were processed by immunohistochemistry （SP） to determine the expression of FHIT genes and p53 protein, by in situ hybridization to detect HPV16/18 infection, and were compared with those in 18 cases of normal cervical tissues as control. Results （1） The FHIT expression was positive in normal cervical tissue with no depletion occurred, and was 30.8% in CIN. It was significantly higher in CIN Ⅲ and carcinoma groups than that in normal and CIN Ⅰ/Ⅱ groups（ P 〈 0.01 ）. The depleted expression of FHIT in infiltrating cervical carcinoma group was 66.7% （46/69） ,significantly higher than that in normal and CIN groups （P 〈0.01 ）. Along with the decreasing of cell differentiation, the negative rate of FHIT raised. （2） The positive expression of p53 in CC group was 56.5% （39/69） and the HPVI 6/18 was 84.1% （58/69）, both higher than that in CIN and normal groups （ P 〈 0.05 ）. （ 3 ） In CIN and CC groups, the positive rate of p53 in cases with positive or negative FHIT expression was similar （P 〉 0.05 ）. （4） There is a negative correlation between FHIT and p53 expression. The rate of HPV16/18 infection in the depleted expression of FHIT group was significantly higher than that in FIHT normal expression group （ P 〈 0.01 ）. Conclusion （ 1 ） The FHIT-depletion is related with cervical carcinogenesis. It may be used as a marker to serve mass screening of CIN-high risk subjects and diagnostic indicator for early cervical carcinoma. （2） Depleted expression of FHIT is frequently associated with p53 over-expression in CIN and CC subjects, but there is no direct correlation between them. （3） HPV16/18 infection may probably be the common cause leading to altered FHIT and p53 expression.