@article{3167155,
    title = "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",
    author = "Kourea, Helen P. and Kotoula, Vassiliki and Koutras, Angelos and and Alexopoulou, Zoi and Papaspirou, Irene and Skarlos, Dimosthenis V. and and Efstratiou, Ioannis and Bobos, Mattheos and Zagouri, Flora and and Papakostas, Pavlos and Pectasides, Dimitrios and Chrisafi, Sofia and and Varthalitis, Ioannis and Aravantinos, Gerasimos and Kosmidis, Paris and and Bafaloukos, Dimitrios and Scopa, Chrisoula D. and Fountzilas, George",
    journal = "HISTOLOGY AND HISTOPATHOLOGY",
    year = "2015",
    volume = "30",
    number = "9",
    pages = "1129-1141",
    publisher = "F HERNANDEZ",
    issn = "0213-3911",
    doi = "10.14670/HH-11-612",
    keywords = "Metastatic breast cancer; Docetaxel; VEGF-A; VEGFR-1; VEGFR-2",
    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, VEGF-C,
thrombospondin-1 (THBS-1), hypoxia-inducible factor-1 alpha (HIF-1
alpha) 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: VEGF-A with VEGFxxxa (rho=0.70); VEGF-C with VEGFxxxa,
VEGFxxxb and VHL (rho=0.51, 0.60 and 0.44 respectively); HIF-1 alpha
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"
}