The Expression Of CXCR4CCR7with Cervical Carcinoma Lymph Node Metastases

Objective：Cervical lymph node metastasis is a complex process, which involve multiple genes.We detect the expression of CXC chemokine receptor4(CXCR4),C-C chemokinereceptor7(CCR7),vascular endothelial growth factor C(VEGF-C) and vascularendothelial growth factor D (VEGF-D) in normal cervix, cervical intraepithelialneoplasia (CIN II-III) and cervical carcinoma. And assess the relationship with clinic-pathological parameters and lymphatic metastasis of cervical carcinoma．Materials and Methods:We use tissue microarray (TMA),The TMA include9cases of normal cervix,2cases of CIN II-III and48cases of cervical cancer.In cervical cancer cases37as I stage，11as II-III stage (staged by International Federation of Gynecology and Obstetrics2009,FIGO2009);33cases of cervical squamous cell carcinoma (CSC),15cases ofcervical adenocarcinoma; Based on the analysis of histological grade，8cases were HG1，38were HG2and8were HG3,1case for limited tissues can not grading;9cases werelymphatic metastasis that confirmed by histological review and39were negative.Immunohistochemical (IHC) staining with the antibodies against CXCR4、CCR7、VEGF-C and VEGF-D were used to examine the expression in normal cervix，cervicalintraepithelial neoplasia(CIN II-III) and invasive cervical carcinoma．By two pathologydoctors in a unified criteria and double blind method to scoring. All statistic analysiswere performed using SPSS16.0． Result：1.The expression of CXCR4, CCR7,VEGF-C and VEGF-D in normal cervix，cervicalintraepithelial neoplasia (CIN II-III) and invasive cervical carcinoma：CXCR4, CCR7were mainly localized in the cytoplasm of the cancer cells andsometimes localized in nucleus. VEGF-C, VEGF-D mostly localized in cytoplasm ofcancer cells，sometimes VEGF-D also localized in nucleus. The positively stained cellsshowed a brown-yellow color.The positive rates of CXCR4were0.00%(0/9),64.58%(31/48) in normal cervix andinvasive cervical carcinoma samples, respectively. There have significant differences ofpositive expressive rates of CXCR4among normal cervix and invasive cervicalcarcinoma samples(P=0.001); The positive rates of CCR7were0.00%(0/9),52.08%(25/48)in normal cervix and invasive cervical carcinoma samples，respectively.There have significant differences of positive expressive rates of CCR7among normalcervix and cervical cancer(P=0.012); The positive rates of VEGF-C were33.33%(3/9),64.58%(31/48)in normal cervix and invasive cervical carcinoma samples，respectively.There were no significant differences of positive expressive rates of VEGF-C amongnormal cervix and invasive cervical carcinoma samples(P=0.167)；The positive rates ofVEGF-D were11.11%(1/9) and47.92%(25/48)in normal cervix and invasive cervicalcarcinoma samples，respectively. There were no significant differences of positiveexpressive rates of VEGF-D among normal cervix and invasive cervical carcinomasamples（P=0.057）. Because of limited CINII-III cases, the expression of CXCR4、CCR7、VEGF-C、VEGF-D can not use statistical analysis. In the2cases of CINII-III,1/2expression CXCR4,1/2expression CCR7,2/2overexpression VEGF-C,1/2expression VEGF-D.2.The expression of CXCR4，CCR7，VEGF-C and VEGF-D in invasive cervicalcarcinoma,and the relationship between tumour markers with cervical carcinomaclinical and pathological parameters：The expression rates of CXCR4were higher in cervical squamous carcinoma thanadenocarcinoma(P=0.002),and the expression rates of CXCR4were higher in carcinoma with lymph node metastasis than which without lymph nodemetastasis(P=0.038),but the expression rates of CXCR4were no differences betweendifferent age, FIGO stage and histological grade (all P>0.05); The expression rates ofCCR7were higher in cervical carcinoma with lymph node metastasis than whichwithout lymph node metastasis(P=0.037), the expression rates of CCR7were nodifferences between different age, FIGO stage,histological grade and pathological type(all P>0.05); The overexpression rates of VEGF-C were higher in II-III stage cervicalcarcinoma than I stage cervical carcinoma (P=0.015), the rates of VEGF-C were alsohigher in cervical carcinoma with lymph node metastasis than which without lymphnode metastasis(P=0.038), but the expression of VEGF-C were not associated with age,histological grade and pathological type (all P>0.05); The expression levels of VEGF-Dwere higher in II-III stage cervical carcinoma than I stage cervical carcinoma(P=0.025), The expression rates were higher in cervical squamous carcinoma thanadenocarcinoma(P=0.017),the rates were also higher in cervical carcinoma with lymphnode metastasis than which without lymph node metastasis(P=0.037), but theexpression rates of VEGF-D were no differences between different age, pathologic stage(all P>0.05).3.With multiple-factor analysis，the expression of CXCR4, CCR7, VEGF-C, VEGF-Dnone is the independent factor of cervical carcinoma Lymph node metastasis（allP>0.05）。4.The correlation between CXCR4，CCR7，VEGF-C and VEGF-D expression rates incervical carcinoma:The expression rates of CXCR4were positive correlated with VEGF-C(r=0.545,P=0.003), VEGF-D (r=0.423,P=0.000), respectively; The expression levels ofCCR7were positive correlated with VEGF-C (r=0.598,P=0.000), VEGF-D (r=0.499,P=0.000), respectively; The expression levels of CXCR4were positive correlated withCCR7(r=0.423,P=0.003); The expression levels of VEGF-C were positive correlatedwith VEGF-D (r=0.510, P=0.000). Conclusion：1.The expression rates of CXCR4in cervical carcinoma were higher than normal cervix，The higher CXCR4expression rates were related with cervical carcinoma pathologicaltype and lymph node metastasis,and irrelevant with age，histological grade andpathological type; The expression levels of CCR7in cervical carcinoma were higherthan normal cervix，the higher CCR7expression rates were closely related with lymphnode metastasis, but irrelevant with age，histological grade and pathological type; Therewere no significant differences of over expressive rates of VEGF-C among normalcervix and invasive cervical carcinoma samples, but the higher VEGF-C overexpression rates were closely related with FIGO stage and lymph node metastasis;There were no significant differences of positive expressive rates of VEGF-D amongnormal cervix and invasive cervical carcinoma samples, but the higher VEGF-Dexpression rates were closely related with FIGO stage,lymph node metastasis andpathological type, respectively.Irrelevant with age，histological grade.2. With multiple-factor analysis，expressive rates of CXCR4,CCR7,VEGF-C,VEGF-Dnone were the independent factor associated of cervical carcinoma Lymph nodemetastasis.3.The expression of CXCR4were positively correlated with VEGF-C, VEGF-D incervical carcinoma, respectively．The expression of CCR7were positively correlatedwith VEGF-C, VEGF-D in cervical carcinoma, respectively; The expression level ofCXCR4were positively correlated with CCR7in cervical carcinoma, The expressionlevels of VEGF-C were positively correlated with VEGF-D in cervical carcinoma,respectively．These suggest CXCR4,CCR7, VEGF-C,VEGF-D may associated with thedevelopment and lymphatic metastasis of cervical carcinoma.