PGF isoforms, PLGF-1 and PGF-2 and the PGF receptor, neuropilin, in human breast cancer: prognostic significance.

Placenta growth factor (PLGF) is a member of the vascular endothelial growth factor (VEGF) family, a group of angiogenic growth factors. Recently, isoforms have been identified. This study examined PLGF-1, PGF-2 and its receptor neuropilin-1 levels in human breast cancer in relation to patient's clinical parameters and how changes in expression may be linked to prognosis of the disease. PLGF-1, PGF-2 and neuropilin-1 transcript expression and distribution were examined quantitatively using real-time quantitative polymerase chain reaction (Q-PCR) on a cohort of human breast cancer (n=114) and background breast tissue (n=30) with a 10-year follow-up. Protein expression was assessed by an immunohistochemical method. We demonstrate that PLGF-1 transcript levels were significantly elevated when comparing tumours from patients with poor outcome and patients who remained disease-free (P=0.03), indicating a potential prognostic value. Immunohistochemistry demonstrated a marked increased in PGF-2 expression in tumour section compared with normal tissues (P<0.05). PGF-2 transcripts, showed little change in expression between tumour and background. High levels of PLGF-1 and PGF-2 were seen in ERbeta-negative breast tumour tissues. Neuropilin transcript was below detection in substantial portion of the samples and was more frequently detected in high grade tumours (P=0.008 vs. low grade) and in tumours from patients who died of breast cancer (P<0.001 vs. those who remained disease-free). Our study shows that PLGF isoforms PLGF-1 and PGF-2 and indeed their receptor neuopilin, have an aberrant pattern of expression and that high levels of the PLGF-1 and neuropilin are linked to a poor prognosis.