Cancer Res Treat.  2008 Sep;40(3):133-140.

Clinical Significance of Vascular Endothelial Growth Factors (VEGF)-C and -D in Resected Non-Small Cell Lung Cancer

• Ko YH
• Jung CK
• Lee MA
• Byun JH
• Kang JH
• Lee KY
• Jo KH
• Wang YP
• Hong YS

Abstract

PURPOSE: Lymphatic spread of tumor is an important prognostic factor for patients with non-small cell lung carcinoma (NSCLC). Vascular endothelial growth factor-C (VEGF-C) and VEGF-D play important roles in lymphangiogenesis via the VEGF receptor 3 (VEGFR-3). We sought to determine whether VEGF-C, VEGF-D and VEGFR-3 are involved in the clinical outcomes of patients with resected NSCLC.
MATERIALS AND METHODS
Using immunohistochemical staining, we investigated the protein expressions of VEGF-C, VEGF-D and VEGFR-3 in the tissue array specimens from patients who underwent resection for NSCLC. The immunoreactivity for p53 was also examined. The clinicopathological implications of these molecules were statistically analyzed.
RESULTS
Analysis of a total of 118 specimens showed that VEGF-C, VEGF-D and their co-expression were significantly associated with more advanced regional lymph node metastasis (p=0.019, p=0.044 and p=0.026, respectively, N2 versus N0 and N1). A VEGFR-3 expression had a strong correlation with peritumoral lymphatic invasion (p=0.047). On the multivariate analysis for survival and recurrence, pathologic N2 lymph node metastasis was the only independent prognostic factor, but none of the investigated molecules showed any statistical correlation with recurrence and survival.
CONCLUSIONS
The present study revealed that high expressions of VEGF-C and VEGF-D were strongly associated with more advanced regional lymph node metastasis in patients with resected NSCLC.

Keyword

Carcinoma; Non-small-cell lung; Vascular endothelial growth factor; Lymphangiogenesis; Neoplasm metastasis

MeSH Terms

Carcinoma, Non-Small-Cell Lung
Humans
Lung
Lymph Nodes
Lymphangiogenesis
Multivariate Analysis
Neoplasm Metastasis
Receptors, Vascular Endothelial Growth Factor
Recurrence
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor C
Vascular Endothelial Growth Factor D
Vascular Endothelial Growth Factor Receptor-3
Vascular Endothelial Growth Factors
Receptors, Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor C
Vascular Endothelial Growth Factor D
Vascular Endothelial Growth Factor Receptor-3
Vascular Endothelial Growth Factors

Figure

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  Fig. 1 Immunohistochemistry for vascular endothelial growth factor C (VEGF-C) and -D and VEGF receptor 3. (A and B) Immuno-reactivity for VEGF-C and -D was detected predominantly in the cytoplasm of the tumor cells; typical examples of VEGF-C (A) and VEGF-D (B) immunopositivity in adenocarcinoma, respectively (×400). (C) Immunoreactivity for the VEGF receptor 3 was detected in the cytoplasm of the stoma cells and tumor cells (×400).

• 

  Fig. 2 Survival curve for patients with non-small cell lung cancer (NSCLC), as stratified by the expression of vascular endothelial growth factor C (VEGF-C; A: overall survival, B: disease-free survival), and the expression of VEGF-D (C: overall survival, D: disease-free survival).

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