Prognostic significance of VEGF receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1) in breast carcinoma

• Published in: Annales de pathologie Vol. 23; no. 4; p. 297
• Main Authors: Dales, Jean-Philippe, Garcia, Stéphane, Bonnier, Pascal, Duffaud, Florence, Carpentier, Séverine, Djemli, Amina, Ramuz, Olivier, Andrac, Lucile, Lavaut, Marie, Allasia, Claude, Charpin, Colette
• Format: Journal Article
• Language: French
• Published: France 01.09.2003
• Subjects: Adult; Aged; Breast Neoplasms - chemistry; Breast Neoplasms - metabolism; Female; Humans; Immunohistochemistry; Middle Aged; Prognosis; Receptors, Vascular Endothelial Growth Factor - analysis; Receptors, Vascular Endothelial Growth Factor - biosynthesis; Vascular Endothelial Growth Factor Receptor-1 - analysis; Vascular Endothelial Growth Factor Receptor-1 - biosynthesis; Vascular Endothelial Growth Factor Receptor-2 - analysis; Vascular Endothelial Growth Factor Receptor-2 - biosynthesis
• ISSN: 0242-6498

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. 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). 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. 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.