Clinical significance of vascular endothelial growth factor-C and vascular endothelial growth factor receptor 3 in patients with T1 lung adenocarcinoma.

BACKGROUND: Vascular endothelial growth factor-C (VEGF-C) plays an important role in lymphangiogenesis and activates VEGF receptor-3 (VEGFR-3). Lymphatic spread is an important prognostic factor in patients with lung adenocarcinoma. The aim of the current study was to determine whether the expression of VEGF-C and VEGFR-3 correlates with clinicopathologic factors and prognosis in patients with TNM classification T1 lung adenocarcinoma.

METHODS: The authors conducted a retrospective review of 129 consecutive patients who underwent complete resection for T1 lung adenocarcinoma. Immunohistochemical staining for VEGF-C, VEGF, VEGFR-3, CD34 (microvessels), tryptase (mast cells), and CD68 (macrophages) was performed to statistically analyze clinicopathologic implications of VEGF-C and VEGFR-3 status.

RESULTS: Of 129 patients with T1 lung adenocarcinoma, 56 (43.3%) patients were positive for tumor-cell VEGF-C and 73 (56.6%) and 69 (53.5%) patients were positive for tumor-cell and endothelial-cell VEGFR-3, respectively. Patients with positive staining for tumor-cell VEGF-C showed significantly less favorable survival rates than patients with negative staining (P = 0.031). The survival rates of patients with positive staining for tumor-cell and endothelial-cell VEGFR-3 were significantly lower than those with negative staining (P = 0.0034 and P = 0.0020, respectively). Patients with positive staining for both tumor-cell VEGF-C and endothelial-cell VEGFR-3 exhibited the most unfavorable prognoses. Multivariate analysis demonstrated that coexpression of tumor-cell VEGF-C and endothelial-cell VEGFR-3 was an independent negative prognostic factor (P = 0.0129) as well as N factor (P = 0.0020).

CONCLUSIONS: VEGF-C and VEGFR-3 status may be indicative of survival rates for patients with T1 lung adenocarcinoma.