[Prognostic significance of VEGF receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1) in breast carcinoma].
OBJECTIVE
The aim of this study was to investigate the prognostic value of vascular endothelial growth factor (VEGF) receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1) in breast carcinoma.


METHODS
VEGF receptor expression was investigated using immunohistochemical assays with monoclonal antibodies on frozen sections in a series of 918 patients and was correlated with prognostic parameters and with long-term follow-up (median, 11.3 years). VEGFR-1 and VEGFR-2 immunostained surface was evaluated in percentage of the total tumor specimen surface by light microscopy (x100).


RESULTS
VEGFR-1 and VEGFR-2 were strongly expressed in endothelial cells within blood microvessels, and weakly in tumor cells. Univariate (Kaplan Meier) analysis showed that VEGFR-1 positive tumor surface (cut off=5%) was not correlated with survival, but was significantly correlated with high metastasis risk (p=0.03) and relapse (p=0.01) in all patients, and in those with node negative tumors (p=0.001 and p=0.01 respectively). In multivariate analysis (Cox model), VEGFR-1 expression was identified as an independent prognostic indicator. Univariate analysis showed that VEGFR-2 positive tumor surface (cut off=10%) was not correlated with survival or with metastasis risk and relapse.


CONCLUSIONS
Our results show that VEGFR-1 immunohistochemical expression permits the identification of patients with poor outcome, particularly those with node negative tumors, with high risk of metastasis and relapse. VEGFR-1 immunodetection may further be considered as a potential tool for evaluating tumor agressiveness and therapeutic strategies in breast cancer.
Dales
Jean-Philippe
JP
Service d'Anatomie et Cytologie Pathologiques, Faculté de Médecine Secteur Nord, Boulevard Pierre Dramard, 13916 Marseille Cedex 20.
Garcia
Stéphane
S
Bonnier
Pascal
P
Duffaud
Florence
F
Carpentier
Séverine
S
Djemli
Amina
A
Ramuz
Olivier
O
Andrac
Lucile
L
Lavaut
Marie
M
Allasia
Claude
C
Charpin
Colette
C
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000032:analysis / Q000096:biosynthesis*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis / Q000096:biosynthesis*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000096:biosynthesis*
D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2