OBJECTIVETo study the relationship between angiogenesis and lymphangiogenesis with the expression of vascular endothelial growth factor C (VEGF-C) and VEGFR-3 in human non-small cell lung cancer (NSCLC).

METHODSSamples of 76 NSCLC cases with the neighboring noncancerous tissue were studied using anti- VEGF-C, VEGFR-3 and CD34 antibodies. Assessment of lymphatic vessel density and microvessel density (MVD) were performed.

RESULTSVEGF-C expression in NSCLC was associating with the differentiation of tumor cells (P = 0.009). Expression of VEGF-C and VEGFR-3 was significantly associated with lymph node metastasis (P = 0.008 and P = 0.013 respectively) and lymphatic invasion (P = 0.027 and P = 0.020 respectively). A significant positive correlation was found between VEGF-C in cancer cells and VEGFR-3 in lymphatic endothelial cells (P = 0.009). The number of lymphatic vessels (P = 0.006) and microvascular (P = 0.046) in VEGF-C positive tumors was significantly larger than in VEGF-C-negative tumors. Lymphatic vessel density was closely related to lymph node metastasis (P = 0.010), lymphatic invasion (P = 0.019) and clinical stages (P = 0.015). MVD was closely related to blood metastasis (P < 0.001) and clinical stages (P < 0.001). Patients with positive VEGF-C expression had a worse prognosis than those with a negative VEGF-C expression (P < 0.001).

CONCLUSIONSVEGF-C/VEGF-D in NSCLCs, are related to lymphangiogenesis and angiogenesis, as well as to the occurrence and the development of lung cancers. VEGF-C promotes intratumoral lymphangiogenesis via VEGFR-3, resulting facilitated invasion of cancer cells into the lymphatic vessels. VEGF-C expression can be a useful predictor of poor prognosis in NSCLC.