Stem cells of the small and large intestine are marked by expression of the Wnt target gene LGR5, a leucine-rich-repeat-containing G protein-coupled receptor. Previous studies reported increased expression of LGR5 in human colorectal cancer (CRC) compared to normal tissue either by immunohistochemistry or in situ hybridization (ISH). However, as these studies were semi-quantitative they did not provide a numerical estimate of the magnitude of this effect. While we confirm that LGR5⁺ cells are exclusively located at the base of normal human small and large intestinal crypts, representing approximately 6% of total crypt cells, we show this cell population is 10-fold expanded in all grades of CRC, representing as much as 70% of the cells of tumor crypt-like structures. This expansion of the LGR5 compartment coincides with maintenance of crypt-like glandular structure (adenomas, and well and moderately differentiated adenocarcinomas), and is reduced in poorly differentiated CRC, where crypt-like glandular architecture is lost, accompanied by reduced epithelial terminal differentiation. Altogether these results indicate that LGR5⁺ cell expansion is a hallmark of CRC tumorigenesis occurring during progression to adenoma, supporting CRC as a stem cell disease with implications for CRC therapy.

小肠和大肠的干细胞以Wnt靶基因LGR5（一种富含亮氨酸重复序列的G蛋白偶联受体）的表达为标志。先前的研究报道，通过免疫组织化学或原位杂交（ISH），与正常组织相比，LGR5在人大肠癌（CRC）中的表达增加。但是，由于这些研究是半定量的，因此没有提供此效应大小的数值估计。虽然我们确认LGR5 ⁺细胞仅位于正常人小肠和大肠隐窝的底部，约占总隐窝细胞的6％，我们显示该细胞群在所有等级的CRC中扩展了10倍，占多达70％的细胞肿瘤隐窝样结构。LGR5区室的这种扩张与隐窝样腺结构（腺瘤以及中分化程度高的腺癌）的维持相吻合，而在分化较差的CRC中，隐窝样腺结构丢失并伴有上皮末端分化减少的情况下，这种情况会减少。总而言之，这些结果表明LGR5 ⁺细胞扩增是在发展为腺瘤的过程中发生CRC肿瘤发生的标志，支持CRC作为一种干细胞疾病，对CRC治疗具有重要意义。