Angiogenesis in resected colorectal liver metastases
2014-12-15T10:34:00Z (GMT) by
Aims: To assess the prognostic significance of angiogenesis using microvessel density (MVD) and angiogenesis-modulating cytokines, in a consecutive series of patients undergoing liver resection for colorectal metastases. Methods: 5 microm sections from formalin-fixed, paraffin-embedded tissue blocks were immunohistochemically stained for microvessels, vascular endothelial growth factor (VEGF) thrombospondin-1 (TSP-1), thymidine phosphorylase (TP) and p53. MVD was measured using a computerised image analysis system. At the edge of the tumour, areas of highest vessel counts or hotspots, and the mean of contiguous x200 high power fields were counted. Within the tumour, hotspots and the random cumulative mean of vessel counts were analysed. The percentage expression of VEGF, TSP-1, TP and p53 was recorded. MVD and the cytokines were correlated using the test. The Kaplan-Meier method, the log rank test, and the Cox proportional hazard model were used to correlate MVD, the cytokines and clinico- pathological variables with patient survival. Results: 182 patients, age range 25-81 (mean 61) were included. On univariate analysis, bilobar disease (p=0.003), tumour edge hotspot (p= 0.005), lymphocytic TP (p=0.02), stromal TSP-1 (p=0.01) and perivascular TSP-1 (p=0.03) significantly correlated with poor prognosis. High expression of TP correlated with high MVD (p=0.04 for hotspots, p=0.001 for contiguous vessels). On multivariate analysis tumour edge hotspot, and bilobar disease were independent prognostic factors (p= 0.038, and p= 0.04 respectively). Conclusion: Thymidine phosphorylase is an important cytokine associated with high tumour edge microvessel density. Tumour edge hotspot and bilobar disease are independent prognostic markers of poor survival in patients who have undergone liver resection for colorectal liver metastases.