Vascular endothelial growth factor expression and microvessel parameters of colonic mucosa correlate with sensitivity to steroid in patients with ulcerative colitis

Abstract

Objective Vascular endothelial growth factor (VEGF) expression and microvessel parameters have not yet been quantified in the colonic mucosa of ulcerative colitis (UC). The aim of this study was to correlate the parameters with clinical responsiveness to steroid therapy.

Material and methods Colorectal biopsy specimens from 39 UC patients with high sensitivity to steroid (H-UC), 9 UC patients with low sensitivity to steroid (L-UC) and 6 normal controls (NC) were examined.

Methods Tissue sections were immunostained with anti-VEGF antibody for number of inflammatory cells (/mm²), VEGF-positive cell (/mm²) and VEGF-positive ratio (%), and with CD34 for microvessel counts (/mm²) and the mean microvessel diameter (μm).

Results The H-UC group had a significantly larger total cell count (10,048±2751, p<0.0001) or VEGF-positive cells (2363±707, p<0.0001) than the NC group (7235±2088 or 1537±297, respectively) with no difference in VEGF-positive ratio (24.3±6.9 for H-UC versus 22.7±6.9 for NC). The L-UC group had a significantly lower VEGF-positive cell count (1420±701, p<0.0005) or VEGF-positive ratio (11.6±5.5, p<0.0005) than the H-UC group, whereas microvessel counts were almost constant regardless of the subject groups (345±7 0 for NC versus 346±99 for H-UC versus 349±114 for L-UC). Significant increases in microvessel diameter were seen when comparing NC (6.68±0.60) with H-UC (7.83±1.09, p<0.0001) and H-UC with L-UC (9.05±1.70, p<0.03). Out of the five parameters, VEGF-positive ratio and microvessel diameter had a predictive value for L-UC with an 88.9% sensitivity and 88.9% specificity.

Conclusions L-UC was characterized either as VEGF underexpression or enlarged microvessel. The disruption of the healing process or disturbance of microcirculation may be involved in low sensitivity to steroid therapy in UC.

• Image processing
• immunohistochemistry
• microvessel
• steroid sensitivity
• ulcerative colitis
• VEGF