5% per year [6]. These and other findings have raised doubt about the relevance of BE as precancerous lesion of EACs (e.g. [7]), stimulation the search for the cell population, from which EACs originate and which is currently unknown. Two cancer models have been put forward to explain tumor heterogeneity and DMXAA clinical trial inherent differences of tumor-regenerating capacity [8]. The clonal selection model of carcinogenesis implies that a random solitary cell undergoes malignant transformation, accumulates multiple mutations and subsequently acquires a survival advantage, which leads to clonal selection [9, 10]. In contrast, the cancer stem cell (CSC) hypothesis regards

malignant transformation as a process, occurring in a subset of normal stem cells with MRT67307 datasheet pluripotent properties, which underlie deregulation of self-renewal pathways selleck screening library [11, 12]. Evidence is accumulating that most, if not all, malignancies are driven by a cancer stem cell compartment [8]. The existence of cancer stem cells would explain why only a small minority of cancer cells is capable of extensive proliferation within the tumor. Furthermore, these cancer stem cells may be inherently resistant to our current therapeutic approaches.

It is important to note that the two models are not mutually exclusive, as CSCs themselves may undergo clonal evolution, as already shown for leukaemia cells [13, 14]. A stem cell hypothesis for BE has also been put forward by the group around Spechler [13]. It has been proposed that specialized intestinal metaplasia could arise from a change in the differentiation pattern of stem cells that might either reside Amino acid in the esophagus or which might be recruited to the esophagus from the bone marrow [13]. A putative intestinal stem cell marker has been proposed to be potentially implicated in carcinogenesis of BE and EAC, but have so far not been thoroughly investigated. Leucine-rich-repeat-containing G-protein-coupled receptor (LgR5) has been shown to be associated with intestinal stem cell properties [15–18]. The aim of our study was to investigate expression of this putative intestinal stem cell marker in esophageal

adenocarcinomas (EAC) with and without associated intestinal metaplasia (BE) as well as associated BE and squamous cell carcinomas. We aimed to give an indication for the carcinogenic process of EACs with respect to a cancer stem cell (CSC) hypothesis. Materials and methods Patients and Tumor Specimen Surgical specimen from altogether 70 patients having undergone primary surgical resection for esophageal cancer between January 2001 and June 2004 with complete (R0) resection, were included in our study. Patients with preoperative antineoplastic therapies (chemoradiation/chemotherapy) were excluded. The material was archival formalin-fixed, paraffin-embedded tissue from routine histopathologic work-up. Formalin-fixation and paraffin-embedding had been performed under standardized conditions.