Prognostic impact of platelet-derived growth factors in non-small cell lung cancer tumor and stromal cells.
BACKGROUND
In tumor angiogenesis there is a complex interplay between endothelial, stromal, and tumor cells (neoplastic epithelial cells). Platelet-derived growth factors (PDGFs) and receptors (PDGFRs) are pivotal in this interaction, and important targets in novel antiangiogenic therapies. This study investigates the prognostic impact of these molecular markers in tumor cells and tumor stroma of resected non-small cell lung cancer (NSCLC) tumors.


METHODS
Tumor tissue samples from 335 resected patients with stage I to IIIA 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, -B, -C, and -D and PDGFR-alpha and -beta.


RESULTS
In univariate analyses, high tumor cell expression of PDGF-B (p = 0.001), PDGF-C (p = 0.01), and PDGFR-alpha (p = 0.026) were negative prognostic indicators for disease-specific survival. In tumor stroma, high expression of PDGF-A (p = 0.009), PDGF-B (p = 0.04), PDGF-D (p = 0.019), and PDGFR-alpha (p = 0.019) correlated with good prognosis. In multivariate analyses, high tumor cell PDGF-B (p = 0.001) and PDGFR-alpha (p = 0.047) expression were independent negative prognostic factors for disease-specific survival, whereas in stromal cells high PDGF-A (p = 0.001) expression had an independent positive survival impact.


CONCLUSIONS
Our results indicate PDGF-B and PDGFR-alpha inhibition as an interesting approach in NSCLC treatment, but also demonstrates the importance of understanding the cellular crosstalk between endothelial, stromal, and tumor cells when targeting PDGF markers.
Donnem
Tom
T
Institute of Clinical Medicine, University of Tromso, Norway. tom.donnem@fagmed.uit.no
Al-Saad
Samer
S
Al-Shibli
Khalid
K
Andersen
Sigve
S
Busund
Lill-Tove
LT
Bremnes
Roy M
RM