新疆维吾尔族妇女宫颈上皮内瘤变及宫颈癌中FHIT、P16^(INK4a)、RARβ蛋白的表达及意义

Expression and significance of FHIT,P16^(INK4a) and RARβprotein in Xinjiang Uygur women cervical intraepithelial neoplasia and cervical cancer

目的探讨脆性组氨酸三联体(fragile histidine triad,FHIT)、P16INK4a与视黄酸受体β(retinoic acid receptor-beta,RARβ)蛋白在新疆维吾尔族妇女宫颈上皮内瘤变(cervical intra-epithelial neoplasia,CIN)及宫颈癌中的表达及其意义。方法采用免疫组化链霉素抗生物素蛋白-过氧化物酶链接(SP)法检测20例慢性宫颈INK4a炎、30例CIN(CINⅠ、CINⅡ、CINⅢ各10例)以及40例浸润性宫颈鳞癌组织标本中FHIT、P16INK4a及RARβ蛋白的表达。结果(1)FHIT蛋白阳性表达率依次为慢性宫颈炎(90.00%)>CIN(66.67%)>浸润性宫颈鳞癌INK4a(27.50%)(P=0.000);P16和RARβ蛋白阳性表达率依次为浸润性宫颈鳞癌(82.50%;90.00%)>CIN(46.67%;53.33%)>慢性宫颈炎(0.00%;10.00%)(P=0.000;P=0.000)。(2)在宫颈各组织中,FHIT蛋白INK4a与P16INK4a蛋白表达呈负相关(r=-0.384,P=0.000);FHIT蛋白与RARβ蛋白表达呈负相关(r=-0.291,P=0.006);P16INK4a蛋白与RARβ蛋白表达呈正相关(r=0.445,P=0.000)。结论抑癌基因FHIT表达缺失与P16INK4a和RARβ过度表达与宫颈癌的发生发展密切相关,并且FHIT、P16INK4a、RARβ具有协同作用。FHIT蛋白与P16INK4a蛋白和RARβ蛋白的联合检测可作为宫颈癌早期诊断和宫颈癌进展的分子指标。

Objective To study the expression and clinical significance of the fragile histidine triad（FHIT）,P16^I NK4a and retinoic acid receptor β（RARβ） protein in the cervical intraepithelial neoplasia（CIN） and cervical cancer of Xinjiang Uygur women.Methods SP method was used to detect the expression of FHIT,P16^ INK4a and RARβ protein in 20 cases of chronic cervicitis,30 cases of CIN（Ⅰtype 10,Ⅱ type 10,Ⅲtype10） and 40 cases of invasive cervical squamous cell carcinoma specimens.Results（1） The order of the positive rate of FHIT protein expression was as follows：in chronic cervicitis（90.00%） 〉in CIN（66.67%）〉 in invasive cervical squamous cell carcinoma（27.50%） with significant differences between them（P=0.000）.The order of the positive rate of P16^ INK4a and RARβ protein was as follows：in invasive cervical squamous cell carcinoma（82.50%;90.00%）〉CIN（46.67%;53.33%）〉chronic cervicitis（0.00%;10.00%） with significant differences between them（P=0.000）.（2） In various cervix uteri tissue,the expression of FHIT and P16 ^INK4a protein was negatively correlated（r=-0.384,P=0.000）,the expression of FHIT and RARβ was negatively correlated（r=-0.291,P=0.006）,the expression of P16 ^INK4a and RARβ protein was positively correlated（r=0.445,P=P0.000）.Conclusion Expression deletion of tumor suppressor gene -FHIT and overexpression P16^ INK4a and RARβ are closely related to the genesis and development of cervical cancer.