?-catenin,LGR5 And GATA6 Are Involved In Colorectal Adenoma-adenocarcinoma Sequence

ObjectiveIn our study,we aimed to investigate the changes and correlations of?-catenin,LGR5 and GATA6 expression during the transition from colorectal normal mucosa to adenoma and adenocarcinoma.MethodsIn sections of a colorectal normal mucosa-adenoma-adenocarcinoma sequence that were obtained from patients with a pathological diagnosis of colorectal adenocarcinoma accompanied by adenoma,immunohistochemistry staining was performed.The expression changes of ?-catenin,LGR5 and GATA6 during the transition from normal mucosa to adenoma and adenocarcinoma were evaluated and correlations were analyzed.Results1.Compared with colorectal normal mucosa,nuclear expression of?-catenin(X2=31.14,P<0.0001)and cytoplasmic expression of LGR5(X2=15.97,P=0.0003)increased in samples of colorectal adenoma and adenocarcinoma,and cytoplasmic expression of GATA6(X2=13.78,P=0.001)increased in samples of adenocarcinoma.However,membrane-bound?-catenin(X2=74.03,P<0.0001)and nuclear GATA6(X2=8.46,P=0.015)expression decreased in samples of colorectal tumor.2.We observed positive correlations between the expression of LGR5 and cytoplamic GATA6 in adenoma(P=0.0005,rs=0.48)and adenocarcinoma samples(P=0.007,rs=0.38),and negative correlation between LGR5 and nuclear GATA6 in adenoma samples(P=0.022,rs=-0.33),but there was no relationship found in normal mucosa(P=0.399).3.Adenomas with mild-grade dysplasia had higher levels of nuclear?-catenin expression compared to adenomas with moderate and severe-grade dysplasia(X2=4.33,P=0.038).When protein expressions were evaluated in adenocarcinomas with different p T stages,we observed a lower nuclear expression of GATA6 in stage T3 and T4 adenocarcinomas compared to stage T1 and T2 adenocarcinomas(X2=5.1,P=0.024).4.The expression of nuclear ?-catenin in samples of adenocarcinoma was significantly increased in the serosa layer compared to other invasive layers of the colorectal wall(X2=8.23,P=0.042).Conclusions1.Increased expressions of ?-catenin in nucleus,LGR5 and cytoplasmic GATA6 and decreased expression of membrane-bound ?-catenin were associated with the transition from normal mucosa through to adenoma and adenocarcinoma.2.LGR5 expression is positively associated with the expression of cytoplasmic GATA6 and negatively correlated with nuclear GATA6.3.Adenocarcinomas with higher expression of nuclear ?-catenin are positively correlated with invasive depth of colorectal wall.