Clinical Study Of The Expression Of Raf Kinase Inhibitor Protein And VEGF-C In Cervical Carcinoma

Objective To detect the expressions of Raf kinase inhibitor protein (RKIP) and vascular epithelial growth factor-C (VEGF-C) in cervical squamous cell carcinoma(SCC) and cervical intraepithelial neoplasia (CIN),so as to investigate the potential clinical significance of the two factors in cervical lesions.in this experiment, we detected the expressions of RKIP and VEGF-C in cervical carcinoma, comparired with clinical stage, pathology classification tried to find out the possible mechanism of RKIP in inhibition of cervical carcinoma.Methods Specimens were collected from 30 cases of patients who suffered from cervical squamous cell carcinoma,30 cases from intraepithelial neoplasia and 20 cases of normal cervical tissues were served as control group.RKIP and VEGF-C were detected immunohistochemically(IHC) with the primary monoclone antibody,rabbit antihuman RKIP antibody and rabbit anti-human VEGF-C.The images were collected with olympus-SPT Image Collected System,and analysed with Mias2000 software for medical application.The density were calssified and the ratio of positive expression cells were evaluated and additioned.Spss10.0 software was adopted in analysis to calculate theχ2 among the group ratio and the correlation between the expression of VEGF-C and RKIP with Pearson and the signifficant was accepted at P<0.05.Results (1)The RKIP positive expression was most evident in normal cervical tissues with a ratio of 85% and decreased in CIN and cervical squamous cell cancer gradually with expression ratio of 60%,30% correspondingly and the differences were significant (P<0.01).(2)the expression of VEGF-C in cervical squamous cell carcinoma was most evident with a positive ratio of 63.3% and the density decreased in CIN and normal cervical tissues with possitive ratio of 50% and 25% and the difference was significant (P<0.01). (3)RKIP expression in well, medium and poor pathologic differentiation were 50%,28.6% and 20% respectively and the difference was significant (P<0.05). While the VEGF-C expression ratio was 50%,64.3%,70% in well,medium and poor-differentiated cervical squamous carcinoma respectively and the difference was significant(P<0.01). (4) In this experiment among 30 cervical squamous cell cancers there were 7 cases with lymph node metastasis, the differences between lymph metastasis positive and negtive were 42.9% and 33.3%,the difference was not signifficant(P>0.05). VEGF-C completely expressed in lymphocyte nodular metastasis group with a ratio of 100% and showed 33.3% in None-lymphocyte nodular metastasis group and the difference was signifficant (P<0.01). (5) RKIP expression I+IIa andⅡb-IV clinical stage were 34.7% and 14.3%, the difference was significant(P<0.05) analysised with Chi-Square Tests.There 11 cases showed negative expression out of 23 cases I+IIa clinincal stage patients with ratio of 52%,in contrast,VEGF-c expressed in all the 7cases ofⅡb-IV stage patients with ratio of 100%. the difference was significant(P<0.05) (P<0.05) (6)The expression of RKIP and VEGF-C showed negatively correlation in cervical lesions (r=-0.385, P<0.01).Conclusion (1) There exist the down-regulation of Raf kinase inhibitor protein in cervical intraepithelial neoplasia and cervical carcinoma, this provide the possibility for the medication of protein kinase inhibitor in the cervical lesions. RKIP delection improved the sensibility of cervical precancerous lesion progressed to cervical squamous cell carcinoma. The down-regulation of RKIP which known as a novel anti-oncogene promote the metastais and restrain differentiation of cervical squamous cell carcinoma.(2)The experiment result show that there existed up-regulation of vascular epithelial growth factor-C cervical intraepithelial neoplasia processing to cervical squamous cell carcinoma.This denote possibe mechanism of VEGF-C acted in cervical carcinoma metastasis.(3) In this experiment the expression of RKIP and VEGF-C showed a negtive correlation, one of the possible expliction is RKIP could inhibit the activation of NF-κB, while the activation of NF-κB up-ragulate the exprssion of VEGF-C which promote the expression of VEGFR3 lead to the growth of vessel and lymph-vessel in tumor tissue and tumor invasion and metastasis.