| Part I Relationships between the expression of CEACAM6ã€FOXP3 and TILs in colon cancer tissues Objective The objective of this study was to explore differences between CEACAM6,FOXP3,TILs and clinicopathological features of colon cancer, further detect the relationship between CEACAM6, FOXP3 expression and T lymphocyte subsets in colon cancer.Materials and Methods Seventy-eight cases of colon cancer including 40 cases of stage I or II and 38 cases of stage III or IV were collected for this study from the First Affiliated Hospital of Soochow University between January 2010 and December 2011. The expression of tumor infiltrating cells(TILs), CEACAM6 and FOXP3 were examined by immunohistochemical analysis.Results In the staging of colon cancer, CD3+T, CD4+T, CD8+T, CD45RO+T were significantly higher in stage I and II compared with stage III or IV(P<0.001, P=0.011,P=0.004, P=0.004, respectively), similarly, T cell infiltrations were higher in better pathological differentiation(P=0.023, P=0.01, P<0.001, P=0.001, respectively). Whereas contrary to CD3+ T, CD4+ T, CD8+ T, CD45RO+ T cell infiltrations in colon cancer, the expression of FOXP3 and CEACAM6 obviously increased in stage III or IV than in stage I or II(P<0.001, P<0.001, respectively), in colon cancer pathology classification, the expression of CEACAM6 has no significant correlation with the pathological grading(P =0.262), while FOXP3 expressed higher in worse pathological differentiation(P < 0.001).Correlation analysis results showed that high FOXP3 expression was significantly associated with low CD3+ T, CD8+ T, CD45RO+ T cell infiltrations(P=0.007, P<0.001,P<0.001, respectively), and high CEACAM6 expression associated with low CD8+ T(P=0.002), CD45RO+ T cell infiltration(P=0.008).Conclusion High expression of CEACAM6 and FOXP3 is associated with poor clinicalpathologic staging and grading, and the overexpression of CEACAM6 and FOXP3 in colon cancer patients plays an important role in the inhibition of cytotoxic and memory T cells. Therefore, the function of CEACAM6 on the regulation of immunity should be taken into account when therapeutic targeting of CEACAM6.Part II Analysis of CEACAM6, FOXP3 expression and TILs in colon cancer Objective To investigate the changes of T cell infiltration density, CECAM6 and FOXP3 expression in normal colon tissues, adenoma and stage I, II and stage III, IV, and further to explore its significance in occurrence and the development of colon cancer.Materials and Methods Seventy-eight cases of colon cancer including forty stage I or II and thirty- eight stage III or IV, thirty cases of adenoma and twelve healthy controls were collected for this study from the First Affiliated Hospital of Soochow University between January 2010 and December 2011. The expression of CD3, CD4, CD8, CD45 RO,CEACAM6 and FOXP3 in colon tissues were examined by immunohistochemical analysis.Development of a RT-PCR assay based on SYBR Green I for detection of CD3, CD4, CD8,CD45 RO, CEACAM6 and FOXP3 m RNA levels in paraffin block specimen.Results CD3+T, CD8+T and CD45RO+T cell infiltrations in colonic adenoma were significantly higher than in normal colon mucosa(P<0.001, P=0.001, P<0.001, respectively)and stage I or II(P = 0.001, P < 0.001, P < 0.001). Agreement with the previous research,the infiltration densities of CD3+ T, CD4+ T, CD8+ T and CD45RO+ T cells were also significantly lower in stage III or IV than in stage I or II(P < 0.001, P = 0.045, P < 0.001, P< 0.001, respectively), and the expression in stage III or IV was obviously lower than in the normal colon tissues(P = 0.015, P = 0.002, P = 0.041, respectively). The expression of CEACAM6 in stage III or IV was higher than stage I or II(P < 0.001), adenoma tissues(P< 0.001) and normal group(P < 0.001), the expression in stage I or II was higher than adenoma(P < 0.001), and the expression in adenoma was higher than the normal tissue(P< 0.001). The expression of FOXP3 in stage I, II and III, IV was significantly higher than normal group(P = 0.014, P < 0.001, respectively), the expression in stage III, IV was higher than in the stage I or II(P < 0.001) and adenoma tissues(P < 0.001). Resultsverification by the method of Real-time PCR and immunohistochemical anlysis are basically identical.Conclusion Our study revealed that CEACAM6, FOXP3 and T cell infiltration were significantly associated with the occurrence and progression of colon cancer. Immune reaction constantly varies between different stages of colon cancer processes. |
