RAF Kinase Inhibitor And Nf-kbp65 Expression And Clinical Significance In Cervical Carcinoma

Objective:To investigate the expression of Raf kinase inhibitor protein (RKIP)and nuclear factor kappa B p65(NF-κBp65) in cervical cancer and to approach the correlation between them and their relationship with clinical-pathologic parameters.Methods:Sixty-nine cases of cervical carcinoma, thirty-seven cases of cervical intraepithelial neoplasia and eighteen cases of normal cervical tissues as control were collected from the affiliated hospital of medical college QingDao university from the year 2006 to 2008.All the cases was confirmed by pathological diagnosis.RKIP and NF-κB p65 were stained immunohistochemically in 69 cases of cervical cancer,37cases of cervical intraepithelial neoplasia and 18 cases of normal cervics,statistical analysis was used to determine the relationship between their expressions and clinicopathological parameters.All statistical analyses were carried out with spssll.5 and ppmsl.5 software. The continuous variables were analyzed with student test,and Spearman's rank correlation coefficient.P<0.05 was considered statistically significant.Results:RKIP protein was predominantly localized in the cytoplasm of the cells.RKIP protein was positively stained in normal cervical tissues, while it was poorly expressed or even not expressed in cervical cancer.NF-κB p65 protein was positively stained in cervical carcinoma and predominantly localized in the cytoplasm of tumor cells. RKIP-positive staining rate in cervical cancer,intraepithelial neoplasia and normal cervics was respectively 29.0%,75.7% and 88.9%,whereas the positive staining rate of NF-κB p65 in cervical cancer,intraepithelial neoplasia and normal cervics was respectively 69.6%,27.0% and 11.1%,,the difference is significant.The expression of RKIP is lower in cervical cancer than cervical intraepithelial neoplasia and normal cervics(Z=-5.159, P=0.000;Z=-5.012,P=0.000),while the expression of NF-κB p65 in cervical cancer is higher than cervical intraepithelial neoplasia and normal cervics(Z=-4.442,p=0.000; Z=-4.309 p=0.000),the differences are significant.The expression of RKIP in cervical cancer was associated with clinical staging,pelvic lymph node metastasis and histopathological grading(respectively X2=5.150, X2=5.555, X2=6.492,P<0.05).The expression of NF-κB p65 in cervical cancer was associated with clinical staging,pelvic lymph node metastasis and histopathological grading(respectively X2=6.574,X2=6.235, X2=11.917, P<0.05)。RKIP expression had negative correlation with NF-κB p65 expression(r=-0.464, P<0.01).Conclusion:The down-regulation or loss of RKIP expression is closely related with cervical cancer development and progression. NF-κB p65 participated in the formation, development and the invasion of cervical carcinoma,The down-regulation or loss of RKIP expression might stimulate migration and metastasis of cervical cancer by up-regulating NF-κB p65 expression. RKIP might be a new target for the therapy of cervical cancer.