Clinical significance of vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 in patients with nonsmall cell lung carcinoma

BACKGROUND: Vascular endothelial growth factor C (VEGF-C) plays an important role in lymphangiogenesis and activates VEGF receptor 3 (VEGFR-3). By contrast, lymphatic spread is an important prognostic factor in patients with nonsmall cell lung carcinoma (NSCLC). The objective 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 primary NSCLC. METHODS: The authors conducted a retrospective review of 180 consecutive patients who underwent complete resection for NSCLC and who did not receive any chemotherapy or radiotherapy prior to surgery. Immunohistochemical staining for VEGF-C and VEGFR-3 was performed. The clinicopathologic implications of VEGF-C and VEGFR-3 expression were analyzed statistically. RESULTS: Of 180 patients with NSCLC, 137 patients (76.1%) were positive for VEGF-C, and 40 patients (22.2%) were positive for VEGFR-3. VEGF-C expression was observed frequently in patients with adenocarcinoma (P = 0.026). For VEGFR-3 expression, significant correlations were demonstrated with age (P = 0.02), gender (P = 0.008), and histologic differentiation in patients with squamous cell carcinoma (P = 0.03). Patients who had positive staining for VEGF-C showed significantly less favorable survival rates compared with patients who had negative staining for VEGF-C (P = 0.003). The survival rates of patients who had positive staining for VEGFR-3 also were significantly lower compared with patients who had negative staining for VEGFR-3 (P < 0.001). Patients who had positive staining for both VEGF-C and VEGFR-3 exhibited the most unfavorable prognoses. Univariate analysis revealed the following prognostic factors: gender (P = 0.03), tumor status (T1,T2 vs. T3; P < 0.01), lymph node status (negative vs. positive; P < 0.01), tumor size (< or = 35 mm vs. > 35 mm; P < 0.01), disease stage (Stage I vs. Stages II and III; P < 0.01), VEGF-C expression (negative vs. positive; P < 0.01), VEGFR-3 expression (negative vs. positive; P < 0.01) and combined VEGF-C and/or VEGFR-3 expression (both positive vs. VEGF-C or VEGFR-3 positive; P < 0.01). Multivariate analysis demonstrated that VEGFR-3 expression was the only independent negative prognostic factor (P < 0.01). CONCLUSIONS: VEGF-C and VEGFR-3 expression may be indicative of survival rates for patients with NSCLC.