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Breast Cancer Research and Treatment

, Volume 133, Issue 1, pp 257–265 | Cite as

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

  • Else Maae
  • Dorte Aalund Olsen
  • Karina Dahl Steffensen
  • Erik Hugger Jakobsen
  • Ivan Brandslund
  • Flemming Brandt Sørensen
  • Anders Jakobsen
Clinical Trial

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.

Keywords

Breast cancer PlGF Prognosis VEGF-A 

Notes

Acknowledgments

This study was enabled by the Department of Surgery, Vejle Hospital, who enrolled the patients. We thank Sara Egsgaard and Camilla Davidsen for their thorough and committed assistance in the laboratory. A special thank to Birthe Østergaard and Anne Marie Bak Jylling for tissue collection.

Conflict of interest

The authors declare no financial conflicts of interest with respect to the authorship and publication of this article.

Ethical standards

This study was approved by the Ethical Committee of Southern Denmark (project identification number VF-20040017) and complies with the Danish low of “Act on Processing of Personal Data” (Act No. 429 of 31 May 2000).

Supplementary material

10549_2012_1957_MOESM1_ESM.pdf (42 kb)
Online Resource 1 Kaplan–Meier RFS for PlGF and VEGF-A in tumor tissue in the subgroups of high-risk patients receiving adjuvant chemotherapy (b,d) and no adjuvant chemotherapy (a, c) (PDF 41 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Else Maae
    • 1
    • 4
  • Dorte Aalund Olsen
    • 2
  • Karina Dahl Steffensen
    • 1
    • 4
  • Erik Hugger Jakobsen
    • 1
  • Ivan Brandslund
    • 2
    • 4
  • Flemming Brandt Sørensen
    • 3
    • 4
  • Anders Jakobsen
    • 1
    • 4
  1. 1.Department of OncologyVejle HospitalVejleDenmark
  2. 2.Department of Clinical BiochemistryVejle HospitalVejleDenmark
  3. 3.Department of Clinical PathologyVejle HospitalVejleDenmark
  4. 4.Institute of Regional Health Services ResearchUniversity of Southern DenmarkOdenseDenmark

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