Association of CD133 expression levels with the k-ras mutation status in rectal cancers before and after preoperative radiochemotherapy.

Abstract

400 Background: The role of the potential stem cell marker CD133 as a predictive or prognostic marker in multimodal rectal cancer treatment is currently under debate. While CD133 has been identified as a prognostic marker in rectal cancers after preoperative radiochemotherapy (RCT) it was recently characterized as a very unspecific feature for colorectal cancer stem cells. We therefore analyzed the association between CD133 expression and mutations in the proto-oncogenes K-Ras and PI3K in rectal cancer patients receiving neoadjuvant RCT. Methods: CD133 expression was evaluated immunhistochemically in pre-treatment biopsies and surgical specimens of 128 patients with locally advanced rectal cancers (cUICC II/III) treated with preoperative RCT within the phase-III German Rectal Cancer Trials. K-Ras mutations were analyzed by sequencing of exons 1, 2, and 3. PI3K mutations were detected by sequencing the p110α subunit (PIK3CA) and correlated with histopathologic parameters, tumor regression and survival. Results: CD133 expression was significantly associated with mutations in the K-Ras gene in both pre-treatment biopsies and post-treatment tumor specimens in uni- and multivariate analyses. However, no significant correlation was observed between CD133 and PI3K mutations. Post-treatment CD133 levels were correlated with neoadjuvant RCT (50.4 Gy/5-FU vs. 50.4 Gy/5-FU+Ox) and tumor regression grading. Anyway, there was no significant association between pre- and post-treatment CD133 expression and disease-free survival. Conclusions: CD133 expression levels are strongly associated with mutations in the K-Ras proto-oncogene in rectal cancers before and after preoperative RCT. Our results strengthen the hypothesis that CD133 is not a specific marker for colorectal stem cells but might be integrated in proliferation pathways like the ras-raf axis.