Direct linear correlation between serum vascular endothelial growth factor (VEGF) and Ki-67 (MIB-1 rate) in women with pT1-2 breast cancer

Background: Several prognostic and predictive factor are available for patients with breast cancer (BC), including the expression of the hormone receptors (luminal vs. non luminal subtypes) and HER2, and the cell proliferation marker Ki-67. Because neoangiogenesis, tumor growth and risk of metastases are strictly interdependent, the role of the vascular endothelial growth factor (VEGF), which is regulator of vascular growth and function, is crucial. Circulating VEGF measurement can be a clinically useful indicator for diagnostic and prognostic evaluation in patients with several solid tumors, including ovarian cancer, hepatocellular carcinoma, and BC. Elevated serum VEGF are currently considered a negative prognostic factor. The aim of this study was to evaluate the relationship between VEGF serum levels and the expression of Ki-67 in patients with BC, hypothesizing that they have the same prognostic value. Materials and Methods: Fifty-nine women (median age 62, range 35-77 years) with pT1-2 pN0 BC who underwent curative surgery and final histological examination were prospectively enrolled in the study. In all patients a commercially available quantitative enzyme-linked immunosorbent sandwich (ELISA) VEGF assay and the Ki-67 expression (evaluated by MIB-1 immunohistochemistry as % of positivity) were available. All the measurements were performed in twice. Results: A very wide variation of values, both as regards the VEGF (median 58, range 5-296 pg/mL) and the MIB-1 (median 12%, range 1-50%), was observed. There was no correlation (p=NS) between the age of the patients and both VEGF (R=0.049) and MIB-1 (R=0.071). However, a strong direct linear relationship between VEGF and MIB1 (R=0.69, p<0.0001, α=4.804, β=0.016, regression line equation: VEGF=4.8041644114118+0.015878493209238 MIB-1) was found.