Expression of LGR5, an intestinal stem cell marker, during each stage of colorectal tumorigenesis.

Background: The Wnt target LGR5 has been recently identified as a murine intestinal stem cell marker. Its role during each stage of human colorectal tumorigenesis remains to be determined. Patients and Methods: LGR5 expression was investigated by immunohistochemical analysis in 17 low-grade and 13 high-grade intraepithelial neoplasias and 30 adenocarcinomas. Results: The number of LGR5-positive cells increased tumor, with clustering of the cells to form patches. An apparent difference in their distribution among the tumorigenesis stages was observed. LGR5 expression in luminal surface showed a negative association with the progressive grade of tumors, while that in lower crypt exhibited a positive association with grade. In adenocarcinomas, LGR5 expression in luminal surface was negatively associated with pStage, while it was almost invariably high in lower crypt during advanced pStage disease. Conclusion: These results suggest that the shifts in the distribution of LGR5-positive cells towards the lower crypt play a role in the development and progression of colorectal cancer. Colorectal cancer is the final stage of a step-wise process that begins with normal tissue, changes to adenoma, followed by the final stage of adenocarcinoma. This process is known as the adenoma-carcinoma sequence, and has been shown to occur in conjunction with the stepwise accumulation of distinct genetic alterations that confer a growth advantage and ultimately contribute to the