Explore The Effectation And Mechanism Of PIK3CA Oncogene Mutation In Colorectal Canceration

ObjectiveExplore PIK3CA mutation in colorectal cancer, detecte PI3Kp110α, p21, Bcl-2 protein expression in different tissues in the progression of colorectal canceration (normal colorectal tissue, colorectal cancer, mild dysplasia adenoma, severe dysplasia adenoma). Analyze the correlation between PIK3CA, PI3Kp110α, P21 and Bcl-2. Explore the effection and mechanism of PIK3CA oncogene in colorectal cancer development, provide not only new marker of diagnose, prognostic, but also new ways treatment for colorectal cancer. Materials and Methods1.Review clinical history ;determine groupsReview archive of pathological data in Affiliated Hospital of Binzhou Medical College Pathology Department during January 2005 to December 2009, according to WHO diagnostic criteria, select 79 cases of colorectal carcinoma, 30 cases of mild dysplasia adenoma, 32 cases of severe dysplasia adenoma, and also 12 cases of normal colorectal tissue as contrast.2.Detected the PI3Kp110αexpression by IHCPI3Kp110αexpression was detected in colorectal cancer, mild dysplasia adenoma, severe dysplasia adenoma, normal colorectal tissue by immunohisto- chemical technique(IHC),Explore its role in progression of colorectal canceration; and further to analyze the correlation between PI3Kp110αexpression and clinical pathologic characteristic of colorectal carcinoma.3.Detected the PIK3CA oncogene mutation by PCRAccording to PI3Kp110αexpression, two groups were divided: positive group and negative group. Detected the PIK3CA oncogene mutation by PCR in defferent groups to explore the correlation with PI3Kp110αexpression. 4.Detected the p21,Bcl-2 expressionDetecte p21, Bcl-2 expression by IHC in colorectal cancer, mild dysplasia adenoma, severe dysplasia adenoma, normal colorectal tissue, analyze the differerce of expression in defferent tissues. explore the correlation with PI3Kp110αexpression, and furthermore explore PIK3CA oncogene mutation cancerigenic mechanisms.Results1. PI3Kp110αexpression have significant difference in defferent tissues In normal colorectal tissue, mild dysplasia adenoma, severe dysplasia adenoma and colorectal cancer, the PI3Kp110αpositive rates were 8.3%, 10%, 34%, 34.5%, the AOD(Average optical density) were 0.0693±0.0062, 0.0738±0.0091, 0.1926±0.0023, 0.1108±0.0032. PI3Kp110αexpression in colorectal cancer and severe dysplasia adenoma were significantly higher than the normal colon tissues and mild dysplasia colorectal adenoma(P﹤0.01).2.Correlation between PIK3CA oncogene mutation and PI3Kp110αexpressionPIK3CA oncogene mutation has correlation with PI3Kp110αexpression, R=0.79, positive group has higher mutation rate than negative group(P<0.01). 3. PI3Kp110αexpression has positive correlation with Bcl-2, but no correlation with p21The correlation between PI3Kp110αexpression and Bcl-2 protein expression is obvious, R=0.53(P<0.01). But no correlation between PIK3CA and p21 protein expression were detected(P﹥0.05).conclusion1. PI3Kp110αis associate with the colorectal cancer progression, PI3Kp110αin severe dysplasia adenoma and colorectal cancer tissues had high expression, and it can be used as a marker for colorectal cancer.2. PIK3CA protein may be a prognostic factor for colorectal cancer ,its expression was associated with the colorectal cancer differentiation ,lymph node status and TNM stage.3. PIK3CA oncogene mutation can up-regulete the expression of PI3Kp110α, its mutation can responsed by expression of PI3Kp110α. 4. The mechanisms of PIK3CA oncogene inducing canceration is that the mutation improve the protein expression and further regulate PI3K/AKT pathway and Bcl-2 expression.5. PIK3CA oncogene mutation play important role in colorectal canceration ,it can induce cell canceration, provide new target for treatment.