Prognostic Significance of Placenta Growth Factor (PlGF)-1 and PGF-2 Expression in Human Breast Cancer.

Abstract

Abstract Background: Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGf) family, a group of angiogenic growth factors important in cancer development. Over-expression of PlGF is known to be associated with pathological angiogenesis. Recently, PlGF has been shown to have 4 isoforms, -1, -2, -3 and -4. This current study examined the expression of PlGF-1 and -2 in human breast cancer and how changes in expression of these isoforms may be linked to prognosis of the disease.Materials and Methods: Breast cancer primary tumours (n=114) and matched background tissue (n=30) were processed for RNA extraction. RNA was reversed transcribed and quantified before analysis by Q-PCR. The results were expressed as copy number of transcript/50ng RNA and standardised using β-actin. Statistical analysis was carried out using student t test (mean±SD) and Mann-Whitney U test (median/IQR) where appropriate. Immunohistochemistry was also carried out on a number of matched background and tumour sections.Results: Analysis of patients with a 10 year follow-up showed that transcript levels of PlGF-1 were increased in node positive tumours when compared to node negative (104.2±52.2 versus 52.5±13.6, respectively, but this did not reach significance(p=0.34). Prognostic indicators (NPI status, TNM status and grade of tumour) were not associated with significant changes in levels of PlGF-1. Moreover, there was no difference in expression with overall ER status of tumours; however, PlGF-1 was significantly increased in ERβ positive tumours (median values ERβ-ive and ERβ+ive (14.10 vs 68.75 respectively, p=0.014). Most interestingly, there was a significant increase in PlGF-1 expression in patients with poor outcome (median values patients remaining disease-free 16.5, patients who died from breast cancer 78.2, p=0.03). In comparison, the PGF-2 isoform showed little change in expression between tumour and background samples. However, Immunohistochemistry demonstrated a marked increased in PGF-2 expression in tumour sections (staining intensity (mean±SD): Background 102.05± 46.65 vs Tumour 172.85±40.33, n=20, p=0.0001).Conclusions: We can conclude from this data that there is a differential expression of the PlGF isoforms in human breast cancer. Inappropriate expression of PlGF isoforms may play a role in human breast cancer progression. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3041.