By applying ROC curve derived cut-off scores to the immunohistochemical markers selleck chemical Wortmannin in this study, we found that VEGF negative tumours were more than four times more likely to undergo a complete tumour regression than their VEGF positive counterparts. Complete pathologic response was nearly six times more likely in EGFR-positive tumours compared with EGFR-negative cases. Moreover, analysis of multi-marker phenotypes of VEGF and EGFR expression identified a subgroup of VEGF-positive and EGFR-negative tumours that were highly resistant to treatment. VEGF is a potent angiogenic promoter required for the full execution of angiogenesis. VEGF receptor signalling has been shown to have effects on endothelial cell proliferation, migration, survival and vascular permeability (Roskoski, 2007).

In addition, urokinase plasminogen activator, tissue plasminogen activator and matrix metalloproteinases are induced by upregulation of VEGF. These proteins function to degrade the basement membrane and extracellular matrix, providing a scaffold for proliferating, migrating and extravasating endothelial cells (Ferrara et al, 2003). The result of tumour angiogenesis is a newly formed vasculature with ��leaky’, disorganised vessels, increased interstitial pressure and chaotic blood flow, which decreases the efficiency of radiotherapy (Willett et al, 2006; Roskoski, 2007). In 1971, Folkman (1971) hypothesised that blocking angiogenesis in tumours could be used a method of treatment for patients with cancer.

Pharmacological agents designed to block VEGF or VEGF receptor signalling are currently in various phases of clinical trials and have demonstrating promising results (Kowanetz and Ferrara, 2006; Roskoski, 2007; Willett et al, 2007). The VEGF blockade results in ��normalisation’ of the vasculature, decreased interstitial pressure and vascular permeability, thereby potentiating the effects of radiotherapy by increasing oxygen transport to tumour cells and facilitating the delivery of chemotherapeutic agents to the target tumour (Willett et al, 2006). In our study, VEGF positivity was strongly associated with a more radio-resistant phenotype. In colorectal cancer, VEGF is associated with tumour aggressiveness, poor survival, local failure and the presence of metastatic disease (Giatromanolaki et al, 2006).

Giralt et al (2007) demonstrated that VEGF positivity is an indicator of poor disease-free survival following preoperative radiochemotherapy, while Nozue et al (2001) described an association between post-treatment VEGF overexpression and distant GSK-3 metastasis. Qiu et al (2000) found no correlation between pretreatment VEGF expression and tumour response in 72 patients undergoing long-course neoadjuvant radiotherapy. In a previous work on the same, yet smaller series of patients, we not only identified VEGF but also Bcl-2 as significant predictors of tumour regression (Zlobec et al, 2005).