Expression of vascular endothelial growth factor-A in human lymph node metastases of prostate cancer

Vascular endothelial growth factors (VEGF) figure among the most potent angiogenic factors identified. Local as well as serum VEGF-A over-expression has been correlated with metastasis in prostate cancer. However, little is known on VEGF-A expression in prostate cancer metastases themselves. Our objective was to assess VEGF-A expression in relation with angiogenesis in prostate cancer lymph node metastases.

Fifty-four lymph node metastatic specimens obtained from 32 patients were included in this study. All nodes were of prostate cancer origin as confirmed by positive PSA staining. Immunohistochemistry was performed to identify VEGF-A expressing cancer cells. Consecutive sections were stained for angiogenesis using von willebrand factor (vWF) as a maker and neuroendocrine (NE) differentiation using chromogranin-A and serotonin antibodies. VEGF-A expressing cells were recorded (at 100x magnification) and expression was classified as: 1- Negative (0 cells), 2-Low (1-5 positive cells/high power field (HPF)), and 3- High (> 5 cells/HPF).

VEGF staining was identified mainly in NE cells and endothelial cells. Of the 32 patients, VEGF expression was positive in 22 (69%), with 2 patients (6%) showing high levels and 20 patients (63%) classified as low. No VEGF expression was noted in 10 patients (31%). Of the 54 metastatic lymph node specimens examined, VEGF expression was positive in 31 (57%). VEGF-A stained NE cells did not correlate with blood vessels as revealed by vWF expression in consecutive sections (p=0.9).

VEGF-A is preferentially expressed in NE cells of prostate cancer lymph node metastases and appears unrelated to angiogenesis. These observations support the role played by NE-expressing VEGF-A in the development of metastatic prostate cancer.