Publication:
Impact of tumor angiogenic profile on the outcome of patients with metastatic breast carcinoma treated with weekly docetaxel. A Hellenic Cooperative Oncology Group (HeCOG) study

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Date
2015
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Authors
Kourea, Helen P. ; Kotoula, Vassiliki ; Koutras, Angelos ; Alexopoulou, Zoi ; Papaspirou, Irene ; Skarlos, Dimosthenis V. ; Efstratiou, Ioannis ; Bobos, Mattheos ; Zagouri, Flora ; Papakostas, Pavlos ; Pectasides, Dimitrios ; Chrisafi, Sofia ; Varthalitis, Ioannis ; Aravantinos, Gerasimos ; Kosmidis, Paris ; Bafaloukos, Dimitrios ; Scopa, Chrisoula D. ; Fountzilas, George
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Publisher
F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología
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DOI
https://doi.org/10.14670/HH-11-612
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info:eu-repo/semantics/article
Description
Abstract
Background: Metronomic taxane administration has putative antiangiogenic properties. Herein, we examined the baseline tumor angiogenic profile of patients with metastatic breast carcinoma (MBC) in a prospective-retrospective translational research study. The interplay between the angiogenic factors expressed in the tumors and their prognostic value in MBC were investigated. Patients and Methods: Tumor tissues from patients with MBC treated with weekly docetaxel (n=159) were examined by immunohistochemistry for VEGF-A, VEGF-C, VEGFR-1, VEGFR-2, VEGFR-3 and osteopontin (OPN) and by mRNA analysis for expression of VEGF-A, VEGFxxxa, VEGFxxxb, VEGFC, thrombospondin-1 (THBS-1), hypoxia-inducible factor-1α (HIF-1α) and von Hippel-Lindau (VHL) genes. Associations between these parameters and outcome were statistically analyzed. Results: Statistically significant correlations were identified between almost all biomarkers examined in continuous form, particularly at the mRNA level: VEGFA with VEGFxxxa (rho=0.70); VEGF-C with VEGFxxxa, VEGFxxxb and VHL (rho=0.51, 0.60 and 0.44 respectively); HIF-1α with VEGF-C and THBS1 (rho=0.48 and 0.45). High VEGF-A mRNA was associated with worse survival (p=0.0279) and marginally with progression free survival (PFS). Intratumoral co-expression of VEGFR-1 and VEGFR-2 proteins was associated with more favorable survival (p=0.0337). In multivariate analysis, only high VEGF-A mRNA levels retained their prognostic role for worse PFS and survival (PFS: HR=2.34, 95% CI=1.25-4.40, p=0.0080; survival: HR=3.15, 95% CI=1.48-6.72, p=0.0029). Conclusions: In MBC, this study confirms the adverse prognostic effect of high intratumoral VEGF-A mRNA and reveals the combined VEGFR-1/VEGFR-2 protein expression as a potentially favorable prognosticator, which merits further evaluation in larger studies.
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Metastatic breast cancer , Docetaxel , VEGFA , VEGFR-1 , VEGFR-2
Citation
Histology and histopathology, Vol. 30, nº 9 (2015)
URI
http://hdl.handle.net/10201/96466
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Histology and histopathology Vol.30, nº9 (2015)
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