VEGF as a predictive marker of rectal tumor response to preoperative radiotherapy

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Abstract
BACKGROUND Neoadjuvant radiotherapy for rectal cancer may result in tumor downstaging or complete tumor regression leading to greater sphincter preservation. The identification of molecular predictive markers of tumor response to preoperative radiotherapy would provide an additional tool for selecting patients most likely to benefit from treatment. The aim of this study was to determine whether VEGF expression in preirradiation tumor biopsies is a useful predictive marker of tumor response in patients with rectal cancer undergoing preoperative radiotherapy. METHODS Immunohistochemistry for VEGF was performed on 59 preirradiation biopsies from patients with completely responsive (ypT0) or nonresponsive tumors after preoperative radiotherapy. VEGF positivity was evaluated using several scoring methods and the association between VEGF and tumor response was compared. The distribution of VEGF scores was obtained as well as the mean VEGF expression in the two response groups. RESULTS The mean VEGF expression in nonresponsive tumors (NR) was significantly greater than in completely responsive tumors (CR) (P = 0.0035). Nearly half (47%) of all CR tumors had a VEGF expression of 10% or less. Eleven tumors were negative (0% immunoreactivity) for the protein and all of these (100%) were complete responders. Fifty-two percent of the NR tumors had VEGF scores of 80% or greater. The four scoring methods used to determine the association between VEGF and tumor response each produced significant results (P < 0.05). CONCLUSIONS The results of this study indicate that VEGF assessed immunohistochemically from preirradiation tumor biopsies may be a useful marker of rectal tumor response to preoperative radiotherapy. Cancer 2005. © 2005 American Cancer Society.