The relationship between lymphangiogenesis and lymph node metastasis in gastric carcinoma

Objective To investigate the relationship between lymphangiogenesis and lymph node metastasis in gastric carcinoma. Methods The expression of VEGF-C mRNA and protein in 5 gastric carcinoma cell lines was examined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Simultaneously, tumor specimens from 3 gastric carcinoma patients with lymph node metastasis paired with their corresponding normal mucosa were examined to verify VEGF-C and VEGFR-3 mRNA expression by RT-PCR. In addition, lymphatic vessel density (LVD) (using an antibody staining podoplanin, a specific marker for lymphatic endothelium) and the expression of VEGF-C protein in tumor tissues of 86 patients with gastric carcinoma were studied by immunohistochemistry. Results !Three of the 5 gastric carcinoma cell lines, ie MKN-45, SGC-7901 and AGS, expressed VEGF-C mRNA and protein; VEGFR-3 mRNA and protein were also fairly expressed in above-mentioned three cell lines. VEGF-C and VEGFR-3 mRNA expression was detected in all gastric carcinomas tissues with lymph node metastasis, and their corresponding normal mucosa tissues but the expression level in corresponding normal tissues was lower than that in tumor tissues. VEGF-C protein was expressed in 66.3% (57/86) of patients. VEGF-C protein expression was more frequently found in tumors with lymph node metastasis than in those without (P0.001). VEGF-C protein expression was also closely related to lymphatic invasion (P0.001) and TNM staging (P0.01). However, there was no significant correlation between VEGF-C expression and age and gender of patients, tumor size, tumor location, histological type, depth of invasion, and distant metastasis. LVD was associated with VEGF-C protein expression (P0.001), lymph node metastasis (P0.01), lymphatic invasion (P0.01), TNM staging (P 0.05), and histological type (P0.05). However, there was no significant correlation between LVD and age and gender of patients, tumor size, tumor location, depth of invasion and distant metastasis. Conclusions!VEGF-C may stimulate lymphangiogenesis in gastric carcinoma through the VEGFR-3 signaling pathway, then enhance the incidence of lymph node metastasis of gastric carcinoma. Thus, lymphangiogenesis may become a newtarget for the treatment of gastric carcinoma.