Abstract 813: Prognostic impact of the expression of cancer stem cell markers CD166, CD44, EpCAM, ALDH1 and CD133 in colorectal cancer

Abstract

Abstract Background: The aim of this study was to elucidate the prognostic impact of the putative cancer stem cell (CSC) markers CD166, CD44s, EpCAM, ALDH1 and CD133 by immunohistochemistry in colorectal cancer and determine their value as potential biomarkers of clinical outcome. Methods: Using the tissue microarray technique, immunohistochemistry was performed on samples from 1420 primary colorectal cancer patients with full clinico-pathological data and 57 normal tissues. Expression was evaluated semi-quantitatively and receiver operating characteristics (ROC) curve analysis was used to identify reliable cut-off scores for positivity. Prognostic effects were subsequently validated using 101 randomly selected whole tissue sections. Invasive potential was tested using 3 colorectal cancer cell lines. Surgically excised colorectal cancer specimens were enzymatically digested and expression of CD166, CD44s and CD133 on tunour cells was evaluated by flow-cytometry. Cells were then injected in limiting amounts s.c. in NOD/SCID mice and allograft outgrowth was monitored by standard methods. Results: A significant increase in CD166, CD44s and CD133 expression and a decreased expression of EpCAM and ALDH1 was noted in tumour compared to normal mucosa (p<0.001, all markers). Loss of membranous CD166, CD44s and EpCAM expression was associated with features of tumour progression, in particular with an infiltrating tumour border configuration (CD166: p<0.001; CD44s: p=0.002; EpCAM:p=0.005). Loss of CD166 and CD44s had a significant negative impact on survival time (p<0.001), which was further confirmed by evaluating corresponding whole tissue sections (p=0.006). CD44-/CD166- cells from 3 colorectal cancer cell lines exhibited in vitro significantly higher invasive potential than their positive counterparts. On the other hand, the ability of cancer cells to initiate tumours in immunodeficient mice was significantly (p=0.03) correlated with their content in CD133+, but not in CD166+/CD44+ cells. Conclusions: Our findings indicate that loss of expression of CD166 and CD44s is linked to an aggressive tumour phenotype and, particularly, to the presence of an infiltrating tumour margin, possibly implicating these proteins in events at the invasive tumour front. Remarkably, the number of CD133+ cells, while important for tumour initiation in immunodeficient hosts, appears to be prognostically irrelevant in possibly immunocompetent patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 813.