Effect Of Expression Of CD10 And Cx43 In Tumor Microenvironment On Cancerized Or Recurrent Colorectal Adenomas

Objective:To investigate the effect of CD10 in tumor-associated fibroblasts(TAFs)and Cx43 on colorectal adenomas and its relation to cancerization and recurrence of adenoma.Methods:Tissue samples of low grade adenoma(n=226),high grade adenoma(n=226)colorectal.adenocarcinoma(n=226)and control were collected.The expression of CD 10 of TAFs and Cx43,P53,Ki-67,CD34,CD31,D2-40,CD4,CD8 and p-catenin in tumor cells were detected by immunohistochemistry.The correlation of CD10-positive TAFs or Cx43-positive tumor cells with the expression of P53,Ki-67,CD34,CD31,D2-40,CD4,CD8 andβ-catenin in tumor tissues was analyzed by Spearmen correlation analysis.The tissue samples of 320 low-grade colorectal adenoma were collected including 188 non-recurrent and 132 recurrent cases(66 cases with low grade adenoma,28 cases with high grade adenoma and 38 cases with colorectal adenocarcinoma),and the expression of CD 10 of TAFs and Cx43 in tumor cells were determined by immunooistochemistry and compared among groups.Results:There was no TAFs in normal colorectal mucosa.The CD 10 expression of TAFs in low-grade adenoma,high-grade adenoma and colorectal adenocarcinoma were 22%,50%,78%,respectively(χ2=33.248,P<0.05),and with a positive corrlation with the expression of p53 and Ki-67(r=0.150,0.144,all P<0.05).The CD10 expression of TAFs was positively correlated with the expression of CD34,CD31and D2-40(r=0.324,0.439 and 0.196,all P<0.05),but wasn’t correlated with the expression of CD4 and CD8(r =0.113 and 0.101,all P>0.05).The positive expression rate of TAFs CD10 was significantly correlated with the sex,age and differentiation degree of colorectal cancer(χ2=5.359,4.869,6.407,all P<0.05),and correlated with the degree of tumor invasion,lymph node metastasis and vascular tumor thrombus(χ2=17.525,11.623,14.848,all P<0.05).What’ more,the expression of CD10 in recurrent colorectal adenocarcinoma was higher than that in recurrent adenoma,and the TAFs CD10 level was signigicantly higher in low and higher-grade adenoma with recurrence than that in without recurrence(χ2=54.174,P<0.05).The expression of TAFs CD10 was a positive corrlation with the expression of β-catenin(r=0.338,P<0.05),but wasn’t correlated with Cyclin D1(r=0.014,P>0.05).Most of Cx43 were found in the cytoplasmic/membrane of normal cell,and the positive rate was 100%.The expression rates of Cx43 in cytoplasmic of low-grade adenoma,high-grade adenoma and colorectal adenocarcinoma were 88%,53%,23%respectively.And the positive expression rate of Cx43 in nuclear of normal cells was 0.The positive expression rate of Cx43 in nuclear of low grade colorectal adenoma,high grade adenoma,and adenocarcinoma was 11%,61%,78%respectively.Futhermore,in nuclear,the expression of Cx43 was a positive corrlation with the expression of Ki-67(r=0.135,P<0.05),CD31(r=0.201,P<0.05),D2-40(r=0.271,P<0.05)and CD4(r =0.131,P<0.05).But the expression of Cx43 wasn’t correlated with p53(r=0.058,P>0.05),CD34(r=0.070,P>0.05)and CD8(r=0.024,P>0.05).What’more,the positive expression rate of Cx43 was significantly correlated with the sex,degree of tumor invasion,the lymph node metastasis and vascular tumor thrombus(χ2=4.232,8.431,13.040,27.375,all P<0.05),but not correlated with age and differentiation degree of colorectal cancer,(χ2=0.650,0.039,all P>0.05).And in nuclear,the expression of Cx43 in recurrent colorectal adenocarcinoma was higher than that in recurrent adenoma,and the Cx43 level was signigicantly higher in low and higher-grade adenoma with recurrence than that in without recurrence(χ2=53.962,P<0.05).Interestingly,in nuclear,the expression of Cx43 was a positive corrlation with the expression of TAFs CD10(r=0.596,P<0.05)and β-catenin(r=0.132,P<0.05),but wasn’t correlated with Cyclin D1(r=0.100,P>0.05).Conclusion:1.Adenomas with high expression of TAFs CD 10 are more prone to recurrence and carcinogenesis.2.The molecule detetion,which is TAFs CD 10 combining with Cx43,p53,Ki67,β-catenin of tumor cell nucleus and CD34,CD 31,d2-40 of tumor cell interstitium,is helpful to diagnose colorectal adenoma carcinogenesis and predicts adenoma recurrence.3.The location changes of Cx43 from the cell membrane to nucleus promote the carcinogenesis and recurrence in the normal mucosal-adenomatous-adenocarcinoma process.