Co-expression of PDGF-B and VEGFR-3 strongly correlates with lymph node metastasis and poor survival in non-small-cell lung cancer.
BACKGROUND
Platelet-derived growth factors (PDGFs) and vascular endothelial growth factors and their receptors [platelet-derived growth factor receptors (PDGFRs) and vascular endothelial growth factor receptors (VEGFRs)] are related to both angiogenesis and lymphangiogenesis and are important targets in new cancer treatment strategies. We aimed to study the PDGFs/PDGFRs and correlations with lymph node metastasis (LNM) and investigate the prognostic impact of the co-expression of PDGF-B and VEGFR-3 and its correlation with LNM.


METHODS
Tumor tissue samples from 335 resected patients with stage I-IIIA non-small-cell lung cancer (NSCLC) were obtained and tissue microarrays were constructed from duplicate cores of tumor cells and tumor-related stroma from each specimen. Immunohistochemistry was used to evaluate the expression of the molecular markers PDGF-A, PDGF-B, PDGF-C, PDGF-D, PDGFR-alpha, PDGFR-beta, VEGFR-3 and D2-40.


RESULTS
There were 232 N0 and 103 N+ patients (76 N1 and 27 N2). In multivariate analyses, high tumor cell PDGF-A expression (P = 0.017) correlated with LNM. Tumor cell co-expression of VEGFR-3 and PDGF-B correlated with nodal metastasis and was an independent indicator of poor prognosis (hazard ratio 4.8, confidence interval 95% 2.80-8.31, P < 0.001).


CONCLUSIONS
Tumor cell PDGF-A expression correlates with LNM, and the co-expression of PDGF-B and VEGFR-3 is strongly associated with poor survival in NSCLC patients.
Donnem
T
T
Department of Oncology, Institute of Clinical Medicine, University of Tromso, Tromso; Department of Oncology, University Hospital of Northern Norway, Tromso. Electronic address: tom.donnem@uit.no.
Al-Saad
S
S
Institute of Medical Biology, University of Tromso, Tromso; Department of Pathology, University Hospital of Northern Norway, Tromso.
Al-Shibli
K
K
Institute of Medical Biology, University of Tromso, Tromso; Department of Pathology, Nordland Central Hospital, Bodo, Norway.
Busund
L-T
LT
Institute of Medical Biology, University of Tromso, Tromso; Department of Pathology, University Hospital of Northern Norway, Tromso.
Bremnes
R M
RM
Department of Oncology, Institute of Clinical Medicine, University of Tromso, Tromso; Department of Oncology, University Hospital of Northern Norway, Tromso.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D012189:Retrospective Studies; D016019:Survival Analysis; D046888:Tissue Array Analysis; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism*
D020574:Proto-Oncogene Proteins c-sis; D040321:Vascular Endothelial Growth Factor Receptor-3