Introduction: Investigation of the role of vascular endothelial growth factor-C (VEGF-C) and VEGF receptor-3 (VEGFR-3) in non-small-cell lung cancer (NSCLC) has mainly focused on lymph node (LN) metastasis related to lymphangiogenesis. However, the coexpression of VEGF-C/VEGFR-3 by tumour cells can independently play an important role. The present study was therefore designed to evaluate VEGF-C/VEGFR-3 coexpression in tumour cells from the primary tumour and corresponding LN metastases.
Methods: VEGF-C and VEGFR-3 expression in cancer cells were evaluated by immunohistochemistry in 92 NSCLC samples and 45 metastatic LNs. Ki67 expression and mitotic index (MI) in tumours and clinicopathological data were analysed concurrently.
Results: VEGFR-3 and VEGF-C expression were observed in 42% and 74% of tumours, respectively. Concurrent expression of VEGF-C and VEGFR-3, observed in 39% of tumours, was significantly associated with a higher proliferation rate and a higher incidence of LN metastases. VEGF-C expression in tumour cells was observed in 100% of metastatic LN and VEGF-C/VEGFR-3 coexpression was observed in 71% of metastatic LN. Finally, concurrent expression of VEGF-C/VEGFR-3 in the primary tumour was associated with poor disease-free survival on univariate analysis.
Conclusion: In NSCLC cancer cells, VEGF-C/VEGFR-3 coexpression suggests an autocrine/paracrine loop responsible for a high proliferation rate in tumour cells. As VEGF-C/VEGFR-3 coexpression is very frequent in metastatic LN tumour cells, it can be hypothesised that this coexpression participates in the growth of LN metastasis.