TY - JOUR
TI - 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
AU - Kourea, Helen P.
AU - Kotoula, Vassiliki
AU - Koutras, Angelos and
AU - Alexopoulou, Zoi
AU - Papaspirou, Irene
AU - Skarlos, Dimosthenis V. and
AU - Efstratiou, Ioannis
AU - Bobos, Mattheos
AU - Zagouri, Flora and
AU - Papakostas, Pavlos
AU - Pectasides, Dimitrios
AU - Chrisafi, Sofia and
AU - Varthalitis, Ioannis
AU - Aravantinos, Gerasimos
AU - Kosmidis, Paris and
AU - Bafaloukos, Dimitrios
AU - Scopa, Chrisoula D.
AU - Fountzilas, George
JO - HISTOLOGY AND HISTOPATHOLOGY
PY - 2015
VL - 30
TODO - 9
SP - 1129-1141
PB - F HERNANDEZ
SN - 0213-3911
TODO - 10.14670/HH-11-612
TODO - Metastatic breast cancer; Docetaxel; VEGF-A; VEGFR-1; VEGFR-2
TODO - 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
ER -