Expressions of vascular endothelial growth factor-C,-D and vascular endothelial growth factor receptor-3 correlates with lymph node micrometastasis of patient with pN0 early gastric cancer

Abstract

Objective To investigate the expressions of vascular endothelial growth factor (VEGF)-C,-D and VEGF receptor-3 (VEGFR-3/Flt-4) in pN0 early gastric cancer (ECG) and their relationship with lymph node micrometastasis.Methods From January 2005 to January 2010,the paraffin-embedded specimens of 61 pN0 ECG were collected.The expressions of VEGF-C,VEGF-D and VEGFR-3 in 61 pN0 early gastric cancer tissue,25 adjacent tissue and CAM5.2 expression in 868 hematoxylin-eosin staining negative lymph nodes were detected by immunohistochemical assay.The rate of lymph node micrometastasis of 61 pN0 ECG was evaluated.According to the data type,t test,x2 test or Fisher exact probability were performed for the relationship analysis between the expressions of VEGF-C,VEGF-D and VEGFR-3 in pN0 stage ECG and lymph node micrometastasis.Results The high expressions of VEGF-C,VEGF-D and VEGFR-3 in the 61 pN0 ECG were 34.4％ (21/61),34.4％ (21/61) and 44.3％ (27/61) respectively,which were higher than those of adjacent tissues [12.0％ (3/25),8.0％ (2/25) and 16.0％ (4/25) respectively] (x2=4.433,6.321 and 6.144 respectively,all P＜0.05).There were 10 cases (16.4％) of pN0 ECG with lymph node micrometastasis.In pN0 ECG,the low expressions of VEGF-C and VEGFR-3 in negative Flt-4 vascular invasion (FVI) were common than positive FVI (x2 =15.828,6.879 and 9.244,all P＜0.05).The high expressions of VEGF-C and VEGFR-3 were related to the depth of tumor invasion (x2 =5.561 and 5.678,both P＜0.05),the density of VEGFR 3 positive vascular (FVD) (t=2.987and 5.652,both P＜0.01) and lymph node micrometastasis (x2 =6.705 and 6.192,both P＜0.05),but not related to the degree of differentiation (P＞0.05).However,the high expression of VEGF-D was not related to depth of tumor invasion,FVD and lymph node micrometastasis (all P＞0.05),but related to the degree of differentiation (x2 =8.472,P =0.004).The high expressions of VEGF-C,VEGF-D and VEGFR-3 were not related to gender,age,tumor location,macroscopic type and tumor size (all P＞0.05).Conclusions The high expressions of VEGF-C,VEGFR-3 were related to lymph node micrometastasis in pN0 ECG.Although the high expression of VEGF-D was not related to lymph node micrometastasis,it could indirectly affect lymph node micrometastasis through VEGF-C-VEGFR-3 axis in pN0 ECG. Key words: Stomach neoplasms; Vascular endothelial growth factor C; Vascular endothelial growth factor D; Receptors; vascular endothelial growth factor; Lymphatic metastasis; Immunohistochemistry