The Effect Of VEGF-C/VEGFR-3 To Lymph Node Metastasis And Prognosis In Intrahepatic Cholangiocarcinoma

Objective: The purpose of this study was to explore the clinicopathological features,surgical techniques and prognostic risk factors of intrahepatic cholangiocarcinoma(ICC).This study is aimed to explore the correlation among tumor-derived VEGF-C/VEGFR-3,lymph node metastasis(LNM),and the prognosis of the patients,and the routine of lymph node metastasis in intrahepatic cholangiocarcinoma.Methods: 104 ICC cases were collected from Jan.2008 to Dec.2013 at Tianjin University Cancer Hospital,and divided into three groups: the hepatic hilum lymphadenectomy(HLL)group,the extended hepatic hilum lymphadenectomy(EHLL)group and the non-lymphadenectomy(NL)group.Their clinical data were retrospectively analyzed,and the prognostic differences were compared among different groups.60 cases of intrahepatic cholangiocarcinoma samples were collected from.Jan.2013 to Dec.2015 at Tianjin University Cancer Hospital.The expression of VEGF-C/VEGFR-3 in paraffin slice was detected using immunofluorescence and we explore the correlation among the co-expression of VEGF-C/VEGFR-3,lymph node metastasis,and the prognosis in ICC.The co-expression of D2-40/Ki-67 in paraffin slice was detected using immunohistochemistry,and we explore the correlation between the regeneration of lymph vessels and the routine of lymph node metastasis in ICC.Results: The 1-,2-and 3-year overall survival(OS)of all cases were 72.1%,56.1% and 43.7%,respectively,and the median survival was 34 months.The 1-,2-and 3-year OS in HLL group were significantly lower than those in NL group(42.9%,28.6% and 28.6% vs 78.9%,62.5%,and 47.8%).The 1-,2-and 3-year OS in EHLL group were not statistically significant with other two groups(75.0%,56.1% and 33.3%).The 1-,2-and 3-year OS in lymph node dissection(LND)group were not statistically significant with the NL group(57.6%?42.4% and 33.9% vs 78.9%?62.5% and 47.8%).In the patients with lymph node dissection,the prognosis of patients with LNM was significantly lower than that of the patients without LNM.In the patients without LNM,there was no statistically significant differences between LND patients and the NL patients.Results of univariate analysis showed that age,gender,American Joint Committee on Cancer(AJCC)stage,differentiation,ferritin(Fer),CA19-9,CEA,LNM and LND were prognostic factors of long-term survival for ICC.Results of multivariate analysis revealed that age,AJCC stage,differentiation,Fer and LNM were independent risk factors of survival.High co-expression of VEGF-C/VEGFR-3 for ICC patients with potentially more LNM and lower prognosis,promoted the proliferation of tumor,and eventually led to the poor prognosis of patients.With the progresses of ICC,the density of microlymphocytes in the tumor microenvironment increases gradually,however,we cannot detect the newborn lymphatic epithelial cells.Conclusions: Prophylactic lymphadenectomy would not be recommended if no LNM existed,however,systematic lymphadenectomy may improved the outcomes of ICC if we identify the location of lymphatic metastasis.Age,AJCC stage,differentiation,Fer and LNM were independent risk factors of survival for ICC.The co-expression of VEGF-C/VEGFR-3 in tumor cells was associated with the clinico-pathological stage and LNM in patients with introhepatic cholangiocarcinoma.High co-expression of VEGF-C/VEGFR-3 indicates the poor prognosis of ICC patients.