title: Prognostic impact of placenta growth factor and vascular endothelial growth factor A in patients with breast cancer.
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.
authors.affiliation: Department of Oncology, Vejle Hospital, Kabbeltoft 25, 7100 Vejle, Denmark. else.maae@slb.regionsyddanmark.dk
authors.forename: Else
authors.initials: E
authors.lastname: Maae
authors.forename: Dorte Aalund
authors.initials: DA
authors.lastname: Olsen
authors.forename: Karina Dahl
authors.initials: KD
authors.lastname: Steffensen
authors.forename: Erik Hugger
authors.initials: EH
authors.lastname: Jakobsen
authors.forename: Ivan
authors.initials: I
authors.lastname: Brandslund
authors.forename: Flemming Brandt
authors.initials: FB
authors.lastname: Sørensen
authors.forename: Anders
authors.initials: A
authors.lastname: Jakobsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000378:metabolism* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D018709:Statistics, Nonparametric; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C000608036:PGF protein, human; D011257:Pregnancy Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor