Most colitis associated carcinomas lack expression of LGR5: a preliminary study with implications for unique pathways of carcinogenesis compared to sporadic colorectal carcinoma

BMC Cancer

Hiroyoshi Ota¹  Takeshi Uehara²  Tomoyuki Nakajima²  Robert Riddell³  James Conner³  Mai Iwaya⁴ 

[1] Department of Clinical Laboratory Sciences, School of Health Sciences, Shinshu University, Matsumoto, Japan;Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano, Japan;Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada;Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada;Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada;Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada;Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano, Japan;

关键词: Inflammatory bowel disease;    Ulcerative colitis;    Crohn’s disease;    Colitis associated colorectal carcinoma;    LGR5;   

DOI  :  10.1186/s12885-021-07835-3

来源: Springer

【 摘 要 】

BackgroundLeucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), a component of the Wnt receptor complex, is thought to lineage label gastric and intestinal stem cells. LGR5 expression is increased in colorectal carcinoma (CRC) compared to normal tissue. Colitis associated colorectal adenocarcinoma (CAC) often shows distinct morphologic and molecular phenotypes compared to sporadic cases. However, the expression profile of LGR5, and by extension the potential role of an intestinal stem cell phenotype, has not been well described in a series of human CAC.MethodRNA in situ hybridization (ISH) for LGR5 expression on 30 CACs (12 cases with conventional morphology and 18 cases with non-conventional type morphology) from 29 inflammatory bowel disease (IBD) patients was performed and compared the expression profile to a control group of 10 sporadic CRCs. Immunohistochemistry for beta-catenin and SATB2 was performed on the 30 CACs.ResultLGR5 was positive in 30% (9/30) of CAC cases and 90% (9/10) of sporadic CRCs (p = 0.002). A large majority (89%) of LGR5 positive CACs were of the conventional histologic type, and conventional type CAC showed a significantly higher LGR5 score (median 3.0; interquartile range 1.75–3.25) than non-conventional type CAC (median 1.5; interquartile range 1.00–2.00) (p = 0.034). CAC with conventional morphology did have a lower level of LGR5 expression than sporadic CRC. Sporadic CRCs showed a significantly higher LGR5 level score than non-conventional type CACs (p < 0.001). Nuclear translocation of beta-catenin was strongly associated with LGR5 expression (p = 0.003), however no significant association was identified between SATB2 expression and LGR5 expression status in CACs.ConclusionThese findings suggest that the wider spectrum of tumor morphology in CAC may be associated with absence of a LGR5-expressing intestinal stem cell phenotype.

【 授权许可】

CC BY