| Background:Lymph node metastasis(LNM) is one of the chief causes of morbidity and mortality in hepatocellular carcinoma(HCC) after hepatectomy. The aim of this study was to evaluate the correlation between protein expression of CXCR4,VEGF-C and CK19 in HCC and LNM,and investigated its relationship to clinicopathological features.Methods:Immunohistochemical study for CXCR4,VEGF-C and CK19 were performed on HCC with(n=123) or without(n=145) LNM using tissue microarrays.The relationship between clinicopathological features and CXCR4, VEGF-C and CK19 were analyzed.Evaluation of immunostaining was performed semiquantitatively by visual assessment.Results:High nuclear CXCR4,VEGF-C,and CK19 expression were correlated with LNM(P＜0.001).High nuclear CXCR4 correlated with VEGF-C expression(correlation coefficient:0.256,P=0.033).High VEGF-C expression was associated with tumor size(P=0.035),vascular invasion(P= 0.010),portal vein thrombosis(PVT)(P=0.019),and UICC T stage(P＜0.001) in HCC patients with LNM.Nuclear CXCR4(AUC:0.695;95%Cl:0.630-0.759; P＜0.001),VEGF-C(AUC:0.629;95%Cl:0.562-0.695;P＜0.001) and CK19(AUC:0.640;95%Cl:0.572-0.707;P＜0.001) expression were predictive LNM from HCC.Patients which tumors with high nuclear CXCR4,VEGF-C or CK19 expression had significantly poorer disease free survival(DFS) and overall survival(OS) than those with low expression(P=0.008 and P=0.002; P=0.005 and P=0.001;P=0.047 and P=0.006;respectively).PVT(RR= 1.732,95%Cl 1.019-2.943,P=0.042),UICC T stage(RR=1.537,95%Cl 1.147-2.059, P=0.004),nuclear CXCR4(RR=1.701,95%CI 1.097-2.637,P=0.018), VEGF-C(RR=1.967,95%CI 1.106-3.500,P=0.021),and CK19(RR=2.114, 95%CI 1.360-3.285,P=0.001) were independent prognostic factors according to multivariate analysis.And UICC T stage(OR=1.589,95%CI 1.282-1.969, P＜0.001),nuclear CXCR4(OR=3.402,95%CI 2.304-5.002,P＜0.001),VEGF-C(OR=1.967,95%CI 1.249-3.096,P=0.003) and CK19(OR=2.659, 95%CI 1.798-3.932,P＜0.001) were independent risk factors for developing LNM.Conclusions:Increased protein expression of nuclear CXCR4,VEGF-C, CK19 and UICC T stage were significantly correlated with LNM and poor outcome in HCC.And they were independent risk factors for developing LNM. Objective The chemokine and bone marrow-homing receptor CXCR4 is implicated in metastases of various cancers.This study was conducted to analyze the association of CXCR4 expression with hepatocellular carcinoma (HCC) bone metastasis and patient survival.Methods Tumor tissue from HCC patients with(n=43) and without(n=138) bone metastasis was subjected to immunohistochemical staining for CXCR4 using tissue microarrays.Immunoreactivity was evaluated semi-quantitatively. A receiver-operating characteristic-based approach and logistical regression analysis were used to determine the predictive value of clinicopathologic factors, including CXCR4 expression,in bone metastasis.Patient survival was analyzed by Kaplan-Meier curves and log rank tests.Results CXCR4 over expression was detected in 34 of the 43(79.1%) patients with bone metastases and in 57 of the 138(41.3%) without bone metastases.CXCR4 expression correlated with(correlation coefficient:0.551, P＜0.001) and was predictive of HCC bone metastases(AUC:0.689;95%CI: 0.601-0.776;P＜0.001).CXCR4 staining intensity was correlated with the bone metastasis-free survival(correlation coefficient:-0.359;P=0.018). CXCR4 over expression in primary tumors(n=91) decreased overall median survival(18.0 months vs.36.0 months,P＜0.001).Multivariable analysis identified CXCR4 as a strong,independent risk factor for HCC bone metastases (OR:5.440;P=0.023) and overall survival(RR:7.082;P=0.001).Conclusions CXCR4 expression in primary HCCs may be an independent risk factor for bone metastasis and may be associated with poor clinical outcome. |
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