宫颈病变组织中MEKK3和TRAIL表达的研究

目的研究有丝分裂原活化蛋白激酶激酶激酶(MEKK3)和肿瘤坏死因子相关凋亡诱导配体(TRAIL)在宫颈病变组织中的表达及其相关性,分析其表达与宫颈癌临床病理特征及预后的关系。方法利用组织芯片技术构建宫颈病变芯片,应用免疫组化En Vision法检测107例宫颈癌、86例宫颈上皮内瘤变(CIN)及35例慢性宫颈炎组织中MEKK3和TRAIL表达水平,同时随访3年以上宫颈癌患者44例,进行生存分析。结果 MEKK3在慢性宫颈炎、宫颈CIN和宫颈癌组织中阳性表达率逐渐升高(P<0.05);宫颈癌组织中TRAIL阳性表达率明显低于宫颈CIN和慢性宫颈炎组织(P<0.05);MEKK3阳性表达率在宫颈癌FIGO分期、浸润深度及淋巴结是否转移阳性率分别递增(均P<0.05),而与患者年龄、组织学类型及分级无关(均P>0.05);TRAIL阳性表达率与宫颈癌组织学分级有关(P<0.05),而与患者年龄、组织学类型、FIGO分期、浸润深度及淋巴结是否转移无关(均P>0.05);MEKK3和TRAIL表达呈负相关(P<0.05);Log-rank分析结果提示MEKK3表达与生存有关(P<0.05),而TRAIL表达与生存无关(P>0.05)。结论 MEKK3和TRAIL异常表达共同参与宫颈癌的发生发展过程,其阳性表达可作为宫颈癌早期诊断及评估生物学行为的分子标志物,MEKK3过表达预示宫颈癌患者不良预后。

The expression of MEKK3 and TRAIL in cervical lesions

Objective To study the expression of MEKK3 and TRAIL in cervical lesions and its correlation,and to explore the relationship between the expression and clinicopathologic features and prognosis.Methods The expression of MEKK3 and TRAIL was detected in 107 cases of cervical carcinoma,86 cases of cervical intraepithelial neoplasia and 35 cases of chronic cervicitis by immunohistochemical En Vision method and tissue microarrays,the prognostic analysis was made in 44 cases who were followed-up for 3 years.Results The expression of MEKK3 increased significantly from samples of chronic cervicitis and cervical intraepithelial neoplasia to cervical carcinoma（P〈0.05）.The positive rate of TRAIL in samples of cervical carcinoma was lower than that in chronic cervicitis and cervical intraepithelial neoplasia（P〈0.05）.The positive rates of MEKK3 were closely related to FIGO stage,infiltration depth and lymphode metastasis of cervical carcinoma（P〈0.05）rather than to age,histological type and grading（P〉0.05）.However,the positive rate of TRAIL was only related to histological grading of cervical carcinoma（P〈0.05）.The expression of MEKK3 was negatively correlated with the expression of TRAIL（P〈0.05）.Log-Rank analysis revealed that it was the expression of MEKK3 not TRAIL which was associated with the survival of patients with cervical cancer（P〈0.05）.Conclusions The abnomal expression of MEKK as well as TRAIL play critical roles in the occurrence and development of cervical carcinoma,which can be served as molecular markers of early diagnosis of cervical carcinoma.Overexpression of MEKK3 indicates an unfavorable prognosis of patients with cervical carcinoma.