Fan et al. BMC Cancer 2011, 11:320 http://www.biomedcentral.com/1471-2407/11/320 R E S E A R C H A R T I C L E Open Access CD133: a potential indicator for differentiation and prognosis of human cholangiocarcinoma Linni Fan1†, Furong He1†, Hongxiang Liu2, Jin Zhu1, Yixiong Liu1, Zhiyong Yin3, Lu Wang1, Ying Guo1, Zhe Wang1, Qingguo Yan1 and Gaosheng Huang1* Abstract Background: CD133 is known to be a cancer stem cell (CSC) marker. However, recent studies have revealed that CD133 is not restricted to CSC but to be expressed not only in human normal tissues but also in some cancers and could serve as a prognostic factor for the patients. Nevertheless, the expression of CD133 in human cholangiocarcinoma (CC) is rare and our study is to detect the expression and explore the potential functions of CD133 in human CC. Methods: Fifty-nine cases, comprised of 5 normal liver tissues and 54 consecutive CC specimens (21 well- differentiated, 12 moderately-differentiated and 21 poorly-differentiated), were included in the study. Immunohistochemical stainning with CD133 protein was carried out, and statistical analyses were performed. Results: CD133 was found to express in all 5 normal livers and 40 out of 54 (74%) CC tissues with different subcellular localization. In the well, moderately and poorly differentiated cases, the numbers of CD133 positive cases were 19 (19 of 21, 90%), 10 (10 of 12, 83%) and 11 (11 of 21, 52%) respectively. Further statistical analyses indicated that the expression and different subcellular localization of CD133 were significantly correlated with the differentiation status of tumors (P = 0.004, P = 0.009). Among 23 patients followed up for survival, the median survival was 4 months for fourteen CD133 negative patients but 14 months for nine CD133 positive ones. In univariate survival analysis, CD133 negative expression correlated with poor prognosis while CD133 positive expression predicted a favorable outcome of CC patients (P = 0.001). Conclusions: Our study demonstrates that CD133 expression correlates with the differentiation of CC and indicates that CD133 is a potential indicator for differentiation and prognosis of human CC. Keywords: CD133, Cholangiocarcinoma, Immunohistochemistry, Differentiation, Prognosis Background CD133, also known as prominin-1, is a five-transmem- brane domain molecule [1,2] located on apical plasma membrane protrusions of embryonic epithelial structures [3-5]. Up to now, it is mainly used for marking stem-like cells of various tissues and cancers [6]. Many tumors are known to contain a minority population of cancer stem cells or tumor-initiating cells which have the properties of self-renewal, proliferation, and multilineage differen- tiation and are responsible for sustaining the tumor [7]. * Correspondence: huanggs@fmmu.edu.cn † Contributed equally 1State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China Full list of author information is available at the end of the article Moreover, CD133 may represent a putative cancer stem cell marker in many solid tumors, such as human colon cancer [8,9], prostate tumor [10,11], pancreatic adenocar- cinoma [12], renal cancer [13], neural tumor [14-17], and hepatocellular carcinoma [18,19]. It has been shown that CD133 is an apical molecule not only in embryonic epithelial structures, but also in many normal human tissues and its expression is not restricted to stem cells in pancreatic tissues [20]. In addition, CD133 has been found to be a prognostic fac- tor of some cancers, such as colon and hepatocellular carcinoma [21,22]. Recently, Shimada et al. reported that normal bile duct epithelia were entirely negative for CD133 while 14 out of 29 CC cases expressed CD133. However, for each case, only a few tumor cells © 2011 Fan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.