Prognostic impact of placenta growth factor and vascular endothelial growth factor A in patients with breast cancer

Breast Cancer Res Treat. 2012 May;133(1):257-65. doi: 10.1007/s10549-012-1957-0. Epub 2012 Jan 22.

Abstract

Placenta growth factor (PlGF) and vascular endothelial growth factor A (VEGF-A) are angiogenic growth factors interacting competitively with the same receptors. VEGF-A is essential in both normal and pathologic conditions, but the functions of PlGF seem to be restricted to pathologic conditions such as ischemic heart disease, arthritis and tumor growth. Angiogenesis is a complex process with several growth factors involved. Because PlGF modulates VEGF-A responses, we investigated their mutual relationship and impact on breast cancer prognosis. Quantitative PlGF and VEGF-A levels were measured in 229 tumor tissue specimen from primarily operated patients with unilateral breast cancer. Non-malignant breast tissue was also dissected near the tumor and quantitative measurements were available for 211 patients. PlGF and VEGF-A protein levels in homogenized tissue lysates were analyzed using the Luminex system. We found significantly higher median levels of PlGF and VEGF-A in tumor tissue compared to non-malignant tissue (PlGF: 69.8 vs. 31.4 pg/mg, p < 0.001 and VEGF-A: 1148.2 vs. 163.5 pg/mg, p < 0.001). PlGF and VEGF-A were correlated in both malignant tissue (r = 0.41, p < 0.001) and in non-malignant tissue (r = 0.69, p < 0.001). The proportion of node positive patients was higher with high PlGF expression (61.4%) than with low PlGF expression (45.6%) in tumor tissue, p = 0.024. High levels of PlGF and VEGF-A in tumor tissue were associated with significant shorter recurrence-free survival (RFS) in both univariate analysis (PlGF: p = 0.023; VEGF-A: p = 0.047) and in multivariate analysis (PlGF: p = 0.026; VEGF-A: p = 0.036). Neither PlGF nor VEGF-A expression in non-malignant tissue were predictors for RFS. In conclusion, our results support the mutual relationship between PlGF and VEGF-A and encourage further investigations as prognostic markers in breast cancer patients.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / surgery
  • Carcinoma, Ductal, Breast / diagnosis
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / surgery
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local*
  • Placenta Growth Factor
  • Pregnancy Proteins / metabolism*
  • Prognosis
  • Proportional Hazards Models
  • Statistics, Nonparametric
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Biomarkers, Tumor
  • PGF protein, human
  • Pregnancy Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Placenta Growth Factor