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

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.