Background: 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 prognosis. Materials and methods: 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. Results: 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) when entered in the model separately, but neither PlGF (p = 0.089) nor VEGF-A (p = 0.127) turned out as independent prognostic variables, when entered in the model together. Neither PlGF nor VEGF-A expression in non-malignant tissue were predictors for RFS. Conclusion: High protein levels of PlGF and VEGF-A seem to be associated with adverse prognosis in breast cancer patients. Our results support the mutual relationship between PlGF and VEGF-A and encourage further investigations as prognostic markers in breast cancer patients.
Placenta growth factor, vascular endothelial growth factor A, breast cancer