The Research On The Role Of EphB/EphrinB In The Pathway Of Canceration Of Serrated Polyps

[Objective]To explore the role of EphB2,EphB4and ligand EphrinB2in the process of colorectal tumorigenesis. We detect the expressions of EphB2,EphB4and its ligand EphrinB2in the normal colon,serrated polyps and colorectal adenocarcinoma through Histological and morphological studies on hyperplastic polyps(HP),traditional serrated adenoma(TSA),sessile serrated adenoma(SSA),colorectal adenocarcinoma.[Material and method]1.Analysis on histomorphological characteristics of SSA We reviewed the colorectal polyps cases detected by electronic colonoscopy in the Binzhou Medical University Hospital from May2006to May2011,checked the integrity of pathological data to determine the patient’s age,gender,endoscopic diagnosis,pathology,pathological diagnosis.According to the diagnostic criteria, screened all slices and made correct diagnosis of hyperplastic polyps,sessile serrated adenomas and traditional serrated adenoma. We paid special attention to the distinction of hyperplastic polyps and sessile serrated adenoma.2.Expressions of EphB2,EphB4and EphrinB2in serrated polyps,colorectal cancer tissues.We detect expressions of EphB2,EphB4and EphrinB2in colorectal cancer of72cases,serrated polyps of61cases(TSA26cases,HP26cases,SSA9cases)and normal colon tissue of33cases through immunohistochemistry,and analyze the correlation of these proteins expression and the relationship with clinicopathological factors.3. Expressions of EphB2,EphB4and EphrinB2in colorectal cancer tissues and colorectal cancer cell lines.①18colorectal cancer tissues and adjacent tissues were used. the expression of EphB2,EphB4and EphrinB2in to mRNA were studied with RT-PCR.②HT-29and SW620were culture in vitro and used for detect EphB2、EphB4、EphrinB2mRNA used with RT-PCR.[Results]1.Clinical pathology and tissue characteristics of serrated polyps We detect85cases of HP in serrated polyps of140cases,accounting for60.7%of serrated polyps;SSA5cases.accounting for3.6%;TSA50cases,accounting for35.7%.80.0%polyps diameter<10mm in HP;more than half polyps diameter<10mm in the SSA and TSA.The HP and TSA is mostly occurs in the rectum and sigmoid colon,the SSA often occurs in the ascending colon and transverse colon.The HP have long and narrow crypt,the upper1/2or1/3have dentelation,no significant cellular atypia.The TSA:the glands have obvious dentelation,significant dysplasia.The SSA/P:have rich dentelation crypt,the bottom of the crypt base was enlarged as the branch-like,inverted"T"type, have mitotic activity in the upper crypt.2.Gene protein expression of EphB2,EphB4and EphrinB2①The EphB2,EphB4and EphrinB2ligand protein are expressed mainly in the membrane and cytoplasm.Positive area of EphB2located in the crypt base and the lower2/3region,Positive area of EphB4and EphrinB2mainly located the whole floor in the crypt,and these three gene protein expression in the jagged structure are intensity greater than the non-serrated like structure of the TSA and HP.②EphB2is expressed in the majority of normal colonic mucosa,and showed a decreasing trend in serrated polyps and colorectal cancer;The positive rate of EphB4and EphrinB2in normal mucosa was lower than in colorectal cancer and serrated polyps(P<0.05).③The expression of EphB2,EphB4and ligand EphrinB2are relevant with tumor differentiation,lymph node metastasis and Dukesstage(P<0.05),and no significant correlation with age,gender,location.④there is certain correlation between the receptor of EphB2,EphB4and ligand EphrinB2(P<0.05).3.Expressions of EphB2,EphB4and EphrinB2①The expressions of EphB2in colorectal cancer tissues were lower than teir adjacent tissues.Yet the lovel of EphB2in well-differentiated carcinoma was higher than poorly-differentiated carcinoma.The expressions of EphB4and EphrinB2were Contrary with EphB2.②The expressions of EphB2、 EphB4、EphrinB2in colorectal cancer cell lines were difference with each other.[Conclusions]1.Histopathological features of serrated polyps shows that it is a group of lesions with a variety of special morphological characteristics,different subtypes have plesiomorphism,have high cancerization potentiality,should be paid more attention.2.EphB2is expressed in the vast majority of normal colon mucosa,differentially expressed in serrated polyps and colorectal cancer.Suggesting that EphB2may inhibit the occurrence and development of colorectal cancer,may become a new target of biological therapy for intestinal tumors,especially colorectal serrated adenocarcinoma.3.Receptor EphB4and its specific ligand EphrinB2and are closely related with tumor occurrence,development,high level expression may promote intestinal tumor growth and metastasisAThe expression of EphB2,EphB4and ligand EphrinB2are correlated with colorectal cancer,suggesting that EphB receptors and ligands EphrinB have independent role and also interaction in the process of tumour generation and development.