Expression of vascular endothelial growth factors-C and -D correlate with evidence of lymphangiogenesis and angiogenesis in pancreatic adenocarcinoma

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Background: We analyzed the intratumoral and peritumoral microvessel density (MVD) and microlymphatic vessel density (MLVD) in pancreatic adenocarcinoma (PAC) and recorded the expression of vascular endothelial growth factor (VEGF)-C and -D. These data were tested for their significance for tumor progression. Methods: The tissue samples were obtained from 30 patients with PAC. The expression of VEGF-C and -D, MLVD, MVD was assayed by immunohistochemical staining. The expression of VEGF-A and -C, and -D mRNA was detected by semi-quantitative RT-PCR. Results: Immunohistochemical analysis revealed the presence of VEGF-C and -D immunoreactivity in 73% (22/30) and 57% (17/30). The positive rates of VEGF-C and -D protein in central portion of tumors (30% and 16.7%) were significantly lower than those in marginal portion (73.3% and 56.7%). The group with high expression of VEGF-C and -D in marginal portion had higher incidence of lymph node metastasis, lymphatic invasion and venous invasion. The MLVD in both of the VEGF-C and -D positive groups was higher than that in the negative groups, and the lymph node metastasis increased. MVD in the VEGF-C positive group was higher than that in the negative group. Conclusions: The expression of VEGF-C and -D in the marginal portion of tumor significantly associated with lymphatic metastasis and prognosis in patients with PAC, and may induced lymphangiogenesis. VEGF-C was important in the regulation of angiogenesis and lymphangiogenesis in PAC.