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Int J Clin Exp Pathol 2011;4(4):327-335

Original Ariticle
Expression of the adult intestinal stem cell marker Lgr5 in the metastatic cascade of
colorectal cancer

Britta Kleist, Li Xu, Guojun Li, Christian Kersten

Department of Pathology and 3Department of Oncology, Soerlandet sykehus HF, Kristiansand, Norway,  Department of Head and Neck
Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.

Received April 3, 2011; accepted April 22, 2011; Epub April 25, 2011; published April 30, 2011

Abstract: The recently advanced cancer stem cell model postulates that progression and metastasis of cancer are mainly driven by tumor cells
with stem cell properties. Intestinal cancer stem cells are difficult to study due to the lack of reliable markers, but expression of the Wnt target
gene Lgr5 is promising to define at least stem cell like cells in intestinal and colorectal cancer. The aim of this study was to find a possible link
of stem cell like cancer cells to the metastatic process of colorectal cancer. To this end, we evaluated immunohistochemical Lgr5 expression
in 31 distant metastases and in primary tumor compartments with relevance for metastasizing, comprising 89 colorectal carcinomas. Lgr5
expression was seen in 51.6% of distant metastases. 12.9%, 14.6% and 26.7% of primary tumors with histologically confirmed tumor buds,
angioinvasion and perineural infiltrates, respectively, showed evidence of Lgr5 expression in these tumor compartments. However, distant
metastases, which were derived from carcinomas with such Lgr5 positive tumor compartments, showed 6- to 11.5-fold higher median value of
Lgr5 expression compared to those metastases derived from tumors without Lgr5 expressing cells in these compartments. These differences
between the metastases were statistically significant, if being related to tumor buds (all tumors; p = 0.047) and to vascular infiltrates (stage IV
tumors; p = 0.007). In conclusion, our results point to rare evidence of Lgr5 positive stem cell like cells in the metastatic cascade of colorectal
cancer, but these few cells might be biologically powerful in the metastatic process of cancer subsets. Clonal analysis is necessary to proof
this hypothesis. (IJCEP1104002)

Keywords: Lgr5, stem cell like cells, tumor compartments, metastasis        

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Address all correspondence to:
Dr. Britta Kleist
Department of Pathology
Soerlandet sykehus HF
4604 Kristiansand, Norway
Tel: +47 3807 3071, Fax: +47 3807 3076