Vascular endothelial growth factor-C and its receptor VEGFR-3 in non-small-cell lung cancer: concurrent expression in cancer cells from primary tumour and metastatic lymph node.
BACKGROUND
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.


CONCLUSIONS
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.
Laboratoire d'Oncologie Cellulaire et Moléculaire, EA 3410, Université Paris 13, Bobigny, France. pierre.saintigny@avc.ap-hop-paris.fr
Pierre
P
Saintigny
Marianne
M
Kambouchner
Madani
M
Ly
Noëlia
N
Gomes
Odile
O
Sainte-Catherine
Roger
R
Vassy
Sébastien
S
Czernichow
Philippe
P
Letoumelin
Jean-Luc
JL
Breau
Jean-François
JF
Bernaudin
Michel
M
Kraemer
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism*
D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3