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LGR5 is known to be a stem cell marker in the murine small intestine and colon, however the localization of LGR5 in human adenoma samples has not been examined in detail, and previous studies have been limited by the lack of specific antibodies. Here we used  in situ  hybridization to specifically examine  LGR5  mRNA expression in a panel of human adenoma and carcinoma samples (n = 66). We found that a small number of cells express  LGR5  at the base of normal colonic crypts. We then showed that conventional adenomas widely express high levels of  LGR5 , and there is no evidence of stereotypic cellular hierarchy. In contrast, serrated lesions display basal localization of  LGR5 , and the cellular hierarchy resembles that of a normal crypt. Moreover, ectopic crypts found in traditional serrated adenomas show basal  LGR5  mRNA, indicating that they replicate the stem cell organization of normal crypts with the development of a cellular hierarchy. These data imply differences in the stem cell dynamics between the serrated and conventional pathways of colorectal carcinogenesis. Furthermore we noted high  LGR5  expression in invading cells, with later development of a stem cell niche in adenocarcinomas of all stages.

Characterization of LGR5 stem cells in colorectal adenomas and carcinomas