BACKGROUND: Lymph node metastasis is an essential determinant for stage and clinical management of non-small cell lung cancer (NSCLC). The vascular endothelial growth factors (VEGFs) and receptors (VEGFRs) are fundamental molecules in angiogenesis and lymphangiogenesis. We aimed to explore the correlations between nodal metastasis and the expression of VEGFs and VEGFRs in tumor cells and in tumor-related stroma. PATIENTS AND METHODS: Tumor tissue samples from 335 resected patients with stage I-IIIA NSCLC were obtained and tissue microarrays were constructed from duplicate cores of tumor cells and surrounding stromal tissue from each resected specimen. Immunohistochemistry was used to evaluate the expression of VEGF-A, VEGF-C, and VEGF-D and VEGFR-1, VEGFR-2 and VEGFR-3. RESULTS: There were 232 N0 and 103 N+ patients (76 N1, 27 N2). In multivariate analyses, low stromal VEGF-A expression (P=0.018) is associated with N+ status. In tumor cells, strong correlations exist between high VEGF-A expression (P=0.032) and N+ status, and high VEGFR-3 expression (P<0.001) and N2-status. CONCLUSION: The converse impact by stromal VEGF-A versus tumor cell VEGF-A expression on nodal metastasis may allude the importance of the tumor-stroma interaction when trying to understand lymphatic metastasis in NSCLC.
BACKGROUND: Lymph node metastasis is an essential determinant for stage and clinical management of non-small cell lung cancer (NSCLC). The vascular endothelial growth factors (VEGFs) and receptors (VEGFRs) are fundamental molecules in angiogenesis and lymphangiogenesis. We aimed to explore the correlations between nodal metastasis and the expression of VEGFs and VEGFRs in tumor cells and in tumor-related stroma. PATIENTS AND METHODS: Tumor tissue samples from 335 resected patients with stage I-IIIA NSCLC were obtained and tissue microarrays were constructed from duplicate cores of tumor cells and surrounding stromal tissue from each resected specimen. Immunohistochemistry was used to evaluate the expression of VEGF-A, VEGF-C, and VEGF-D and VEGFR-1, VEGFR-2 and VEGFR-3. RESULTS: There were 232 N0 and 103 N+ patients (76 N1, 27 N2). In multivariate analyses, low stromal VEGF-A expression (P=0.018) is associated with N+ status. In tumor cells, strong correlations exist between high VEGF-A expression (P=0.032) and N+ status, and high VEGFR-3 expression (P<0.001) and N2-status. CONCLUSION: The converse impact by stromal VEGF-A versus tumor cell VEGF-A expression on nodal metastasis may allude the importance of the tumor-stroma interaction when trying to understand lymphatic metastasis in NSCLC.
Authors: Elena V Kurenova; Darrell L Hunt; Dihua He; Ann D Fu; Nicole A Massoll; Vita M Golubovskaya; Christopher A Garces; William G Cance Journal: Cell Cycle Date: 2009-07-23 Impact factor: 4.534
Authors: Tom Donnem; Christopher G Fenton; Kenneth Lonvik; Thomas Berg; Katrine Eklo; Sigve Andersen; Helge Stenvold; Khalid Al-Shibli; Samer Al-Saad; Roy M Bremnes; Lill-Tove Busund Journal: PLoS One Date: 2012-01-25 Impact factor: 3.240
Authors: T Sasahira; M Kurihara; U K Bhawal; N Ueda; T Shimomoto; K Yamamoto; T Kirita; H Kuniyasu Journal: Br J Cancer Date: 2012-07-26 Impact factor: 7.640
Authors: Thomas K Kilvaer; Erna-Elise Paulsen; Sigurd M Hald; Tom Wilsgaard; Roy M Bremnes; Lill-Tove Busund; Tom Donnem Journal: PLoS One Date: 2015-08-25 Impact factor: 3.240