the spatial distribution of lgr5+ cells correlates with gastric cancer progression的空间分布lgr5就+细胞与胃癌进展.pdfVIP

The Spatial Distribution of LGR5+ Cells Correlates With Gastric Cancer Progression 1 1 ¨ 1 1 1 2 Eva Simon , Diana Petke , Christine Boger , Hans-Michael Behrens , Viktoria Warneke , Matthias Ebert , ¨ 1* Christoph Rocken 1 Institute of Pathology, Christian-Albrechts-University, Kiel, Germany, 2 Department of Medicine II, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany Abstract In this study we tested the prevalence, histoanatomical distribution and tumour biological significance of the Wnt target protein and cancer stem cell marker LGR5 in tumours of the human gastrointestinal tract. Differential expression of LGR5 was studied on transcriptional (real-time polymerase chain reaction) and translational level (immunohistochemistry) in malignant and corresponding non-malignant tissues of 127 patients comprising six different primary tumour sites, i.e. oesophagus, stomach, liver, pancreas, colon and rectum. The clinico-pathological significance of LGR5 expression was studied in 100 patients with gastric carcinoma (GC). Non-neoplastic tissue usually harboured only very few scattered LGR5+ cells. The corresponding carcinomas of the oesophagus, stomach, liver, pancreas, colon and rectum showed significantly more LGR5+ cells as well as significantly higher levels of LGR5-mRNA compared with the corresponding non-neoplastic tissue. Double staining experiments revealed a coexpression of LGR5 with the putative stem cell markers CD44, Musashi-1 and ADAM17. Next we tested the hypothesis that the sequential changes of gastric carcinogenesis, i.e. chronic atrophic gastritis, intestinal metaplasia and invasive carcino