Study On The Function Of Lymphangiogenesis In Gastric Carcinoma Invasion And Metastasis

Objective To test the expression of Vascular endothelial growth factor C（VEGF-C）,vascular endothelial growth factor receptor-3(VEGFR-3), lymphatic vessel hyaluronanreceptor-1(LYVE-1) in gastric carcinoma and lymph nodes, and analyze the relationship ofwith their clinical and pathological characteristics and metastasis and prognosis of gastriccarcinoma, and Compare the expression of the three indicators in gastric carcinoma andlymph node metastasis,meanwhile to test lymphatic vessel density (LVD), and to explore theregulation of VEGF-C, VEGFR-3and LYVE-1in gastric cancer development and invasionand metastasis, evaluate whether they can be used as molecular biological markers ofpredicting gastric cancer invasion,metastasis and prognosis.Methods Application of Tissue Microarray technology, Tissues of125gastriccarcinoma patients and including96cases of adjacent normal tissue (from cancer tissue≥5cm) and20patients with benign gastric lesion in the affiliated hospital of Ningxia medicaluniversity from Jan2005to Dec2009were detected by Immunohistochemistry(IHC)technique for analysis of VEGF-C, VEGFR-3and LYVE-1and the600lymph nodes aroundGastric cancer, Podoplanin marks lympgatic vessel.Results1)The positive expression rate of VEGF-C, VEGFR-3and LYVE-1in gastriccarcinoma tissue were62.4%,56.0%and58.4%;69.0%,65.0%and62.0%in metastatic lymphnodes;10.41%,12.50%and9.375%in adjacent normal tissue;20.00%,、30.0%and25.0%inbenign gastric lesion tissue. There was no significant difference between the positiveexpression rates of VEGF-C, VEGFR-3and LYVE-1in metastatic lymph nodes and in gastriccarcinoma tissu（eP＞0.05）.Compared the expressions of VEGF-C, VEGFR-3and LYVE-1ingastric carcinoma tissue with adjacent normal tissue and benign gastric lesion tissue, there were all significant differences (P<0.05); The positive expression rates of VEGF-C,VEGFR-3and LYVE-1in no metastatic lymph nodes were51.0%（153/300）,47.0%（141/300）,48.0%（144/300）.2) The positive expression rates of two or three coexpressionwere significantly higher than single expression in gastric carcinoma tissue and in lymphnodes, there were significant statistics differences between them(P<0.05).3) The expressionof VEGF-C, VEGFR-3and LYVE-1were all positively correlated with LVD in gastriccarcinoma tissue and in lymph nodes (P<0.05).4) The positive expression rates of VEGF-Cand LYVE-1were significantly correlated with depth of invasion, lymph node metastasis,distant metastasis and clinical stage (P<0.05) in gastric carcinoma patients; The positiveexpression rates of VEGFR-3were significantly correlated with distant metastasis and clinicalstage (P<0.05); Multivariate logistic regression analysis showed that distant metastasis andclinical stage were related to the expression of VEGF-C, VEGFR-3and LYVE-1incorrelation (P<0.05); depth of invasion was related to the expression of VEGFR-3(P<0.05).5) The expression of VEGF-C were positively correlated with CEA; the expression ofVEGFR-3and LYVE-1were positively correlated with CEA and CA19-9. In theCEA-negative patients with gastric cancer,the positive expression rates of VEGF-C,VEGFR-3and LYVE-1were59.09%(26/44),50.00%(22/44) and40.91%(18/44); In theCA19-9negative patients with gastric cancer,the positive expression rates of VEGF-C,VEGFR-3and LYVE-1were64.29%(36/56),60.71%(34/56) and50.00%(28/56).6)Kaplan-Meier survival analysis showed that: VEGF-C, VEGFR-3and LYVE-1expressionwere significantly correlated with OS, the5-year survival rates in negative expression patientswere significantly higher than those of positive expression (P<0.05). The positive expressionrates of VEGF-C, VEGFR-3and LYVE-1were all significantly different in recurrencemetastasis and unrecurrence metastasis in five years after the radical mastectomy.7) Theexpression of VEGF-C, VEGFR-3and LYVE-1in gastric tissue were all positively correlatedwith each other.8）The expression of VEGF-C, VEGFR-3and LYVE-1which were detected in gastric carcinoma patients with sensitivity of75.00%~89.28%, specificity of58.33%~75.00%, accuracy of75.00%~80.00%. There was no significant difference betweenthe VEGF-C,VEGFR-3and LYVE-1of the sensitivity, specificity, accuracy, positivepredictive value and negative predictive value（P＞0.05）.Conclution (1) VEGF-C, VEGFR-3and LYVE-1protein positively highly expressedin gastric carcinoma tissue and were positively correlated with LVD. With clinical stage,recurrence and metastasis and survival, suggested that they were closely related to thebiological behavior of gastric cancer,so they can be used as a molecular biology marker topredict early onset of gastric cancer invasion,metastasis and prognosis.(2)There existed singleand coexpression of VEGF-C, VEGFR-3and LYVE-1protein in gastric carcinoma tissue andin lymph nodes, Mainly coexpression, and between every two expression was positivelycorrelated, indicated that all of them were involved in lymphangiogenesis of gastric cancer,and there was a synergistic rolein this processcom, Suggested that tumor lymphangiogenesisis more than one factor involved in the complex process of, The combined detection of avariety of lymphangiogenesis factors may increase the detection rate of lymph nodemetastasis.(3) The expression of VEGF-C, VEGFR-3and LYVE-1were positively correlatedwith CEA and CA19-9in gastric cancer, Suggested that the high expression of VEGF-C,VEGFR-3and LYVE-1may be the biological parameter of judging gastric cancer invasion andmetastasis. The three factor detection of negative expression of CEA and CA19-9mayincrease the early detection rate of invasion and metastasis.(4) Diagnostic tests by clinicalepidemiological evaluation of VEGF-C、VEGFR-3and LYVE-1can be generated as adiagnosis of gastric cancer patients with micro-lymphatic tube and predict the lymphaticmetastasis indicators, the three detection performance similar to.