This protein, however, was not associated with complete tumour regression in this study, a discrepancy that is likely due to the different clinical endpoints evaluated in our previous and current works. These inhibitor Pazopanib results suggest a possible role for Bcl-2 in tumour regression, which requires further elucidation. To our knowledge, the present study is the first to have evaluated complete pathologic response and pretreatment VEGF expression in rectal tumours. Our results clearly demonstrate that patients with VEGF-negative tumours before treatment should be considered candidates for preoperative radiotherapy. Although the prognostic role of EGFR has been frequently investigated, only few studies have assessed the predictive value of pretreatment EGFR expression in preoperative radio- or radiochemotherapy.

Recent reports are conflicting. While Giralt et al (2005) found a significant association between EGFR overexpression and a lack of complete pathologic tumour regression to preoperative radiotherapy, Bertolini et al (2007) reported no such result. The findings of our study indicate that pretreatment EGFR expression is an indicator of complete pathologic response and strongly supports the treatment of these patients with preoperative radiotherapy. Recently Jonker and co-workers assessed the value of the anti-EGFR therapy cetuximab on a large cohort of 572 patients with advanced EGFR-expressing colorectal cancers who failed to respond to previous chemotherapy, and found a significant improvement in overall survival in these patients.

Anti-EGFR therapy may further improve clinical outcome in our series our EGFR-positive, and more radiosensitive patients treated with HDREB (Jonker et al, 2007). Although our results, which indicate improved outcome in patients with positive EGFR, appear to conflict with the majority of reports in colorectal cancer, our findings are in line with previous studies in head and neck squamous cell carcinoma (HNSCC) using moderately accelerated or hyperfractionated accelerated radiotherapy. Eriksen et al (2005) investigated 803 patients randomised to 5 vs 6 fractions per week of radiotherapy. They found that high-EGFR tumours responded better to moderately accelerated radiotherapy compared with EGFR-low tumours, and determined that response to accelerated fractionation may be predicted by high EGFR expression in pretreatment tissue samples.

Bentzen and co-workers performed IHC on 304 patients randomised to receive CHART vs conventionally fractionated radiotherapy. They concluded that there was a significant benefit from strongly accelerated CHART in patients with high EGFR expression and no benefit in patients Batimastat with a low EGFR index (Bentzen et al, 2005). These results suggest that the predictive value of EGFR to radiotherapy may be dependent on the dose fractionation regimen.