Distribution of intestinal stem cell markers in colorectal precancerous lesions

<jats:sec><jats:title>Aims</jats:title><jats:p>Intestinal stem cell (<jats:styled-content style="fixed-case">ISC</jats:styled-content>) markers such as <jats:italic><jats:styled-content style="fixed-case">LGR</jats:styled-content>5</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">ASCL</jats:styled-content>2</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">EPHB</jats:styled-content>2</jats:italic> and <jats:italic><jats:styled-content style="fixed-case">OLFM</jats:styled-content>4</jats:italic>, and their clinical implications have been studied extensively in colorectal cancers (<jats:styled-content style="fixed-case">CRC</jats:styled-content>s). However, little is known about their expression in precancerous lesions of <jats:styled-content style="fixed-case">CRC</jats:styled-content>s. Here, we investigated the expression and distribution of <jats:styled-content style="fixed-case">ISC</jats:styled-content> markers in serrated polyps and conventional adenomas.</jats:p></jats:sec><jats:sec><jats:title>Methods and results</jats:title><jats:p>Reverse transcription–polymerase chain reaction (<jats:styled-content style="fixed-case">RT</jats:styled-content>–<jats:styled-content style="fixed-case">PCR</jats:styled-content>) analysis revealed that all <jats:styled-content style="fixed-case">ISC</jats:styled-content> markers were up‐regulated significantly in conventional adenomas with low‐grade dysplasia (<jats:styled-content style="fixed-case">CALG</jats:styled-content>s) compared with other lesions. <jats:styled-content style="fixed-case">RNA </jats:styled-content><jats:italic>in‐situ</jats:italic> hybridization confirmed that <jats:styled-content style="fixed-case">CALG</jats:styled-content>s exhibited strong and diffuse expression of all <jats:styled-content style="fixed-case">ISC</jats:styled-content> markers, which indicate a stem cell‐like phenotype. However, normal colonic mucosa, hyperplastic polyps and sessile serrated adenomas harboured <jats:italic><jats:styled-content style="fixed-case">LGR</jats:styled-content>5</jats:italic><jats:sup><jats:italic>+</jats:italic></jats:sup> cells that were confined to the crypt base and demonstrated an organized expression of <jats:styled-content style="fixed-case">ISC</jats:styled-content> markers. Notably, in traditional serrated adenomas, expression of <jats:italic><jats:styled-content style="fixed-case">LGR</jats:styled-content>5</jats:italic> and <jats:italic><jats:styled-content style="fixed-case">ASCL</jats:styled-content>2</jats:italic> was localized to the ectopic crypts as in the normal crypts, but expression of <jats:italic><jats:styled-content style="fixed-case">EPHB</jats:styled-content>2</jats:italic> and <jats:italic><jats:styled-content style="fixed-case">OLFM</jats:styled-content>4</jats:italic> was distributed in a diffuse manner, which is suggestive of a progenitor‐like features.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The expression and distribution profile of <jats:styled-content style="fixed-case">ISC</jats:styled-content> markers possibly provides insights into the organization of stem and progenitor‐like cells in each type of precancerous lesion of <jats:styled-content style="fixed-case">CRC</jats:styled-content>.</jats:p></jats:sec>