| Objective: Colorectal adenoma is the most common colon benign lesion with a higher incidence. As one of the main precancerous lesions of colorectal carcinoma, tubular adenoma is the most common histological type. In clinical, sporadic tubular adenoma canceration is not rare and it has a complex mechanism. Despite the mechanism is not clear and lack of systemic research, it has a wide explorated prospect.In the last twenty years,our research group has been committed to sporadic colorectal tubular adenoma and the mechanism of the adenoma canceration, especially the Wnt/?-catenin signaling pathway. Previous studies showed that factors such as RUNX3 and HMGA2 could participate in the development and progression of sporadic colorectal tubular adenoma canceration by regulating the Wnt/?-catenin signaling pathway, whose mechanism is very complicated. Research showed that Insulin-like growth factor binding protein 4(IGFBP-4) could interacte with Frizzled 8 to Wnt in the process of cell development to inhibite the cell differentiation by making Wnt pathway inactivation. This gave us a possibility if IGFBP-4 could play a role through Wnt/?-catenin in the carcinogenesis of sporadic colorectal tubular adenoma. We did not see the reports at home and abroad.On the basis of previous study, we analysised the effect of IGFBP-4 and Wnt/?-catenin signal pathway correlated factors(Wnt, ?-catenin, Frizzled8, CDK2 and Cyclin B1) in the sporadic colorectal tubular adenoma canceration from histologic aspect and their relationship with clinical pathological features,and explored the possible role of IGFBP-4 in sporadic colorectal tubular adenoma canceration which is mediated by the Wnt/?-catenin signaling pathway.Methods:1 We used immunohistochemical ElivisionTMplus method to study the expression of IGFBP-4, Wnt, ?-catenin, Frizzled8, CDK2 and Cyclin B1 in 33 cases of normal colorectal mucosa, 96 cases of sporadic colorectal tubular adenoma with different dysplasia and 82 cases of colorectal tubular adenoma with carcinomatous changes. And we discussed the correlation between IGFBP-4 and indexes, and correlation analysis combined with clinical pathological characteristics.2 SPSS16.0 software was applicated. The experimental data were analyzed by Chi-square test, Fisher's exact test and spearman correlation analysis.Results:1 Immunohistochemical results1.1 The expression of IGFBP-4 in the process of colorectal adenoma carcinomatousImmunohistochemical results showed that the positive expression rate gradually decreased in normal colorectal mucosa, tubular adenoma with varying degrees dysplasia and colorectal carcinoma changed from tubular adenoma(78.8%, 58.3%, 39.0%, P<0.05). The expression of IGFBP-4 in normal colorectal mucosa is significantly higher than that in the other groups(P<0.05). The expression of IGFBP-4 in tubular adenoma is higher than that in colorectal carcinoma(P<0.05). The positive expression rate gradually decreased in tubular adenoma with varying degrees dysplasia(67.7%, 65.7%, 40.0%, P<0.05). The expression of IGFBP-4 in sporadic colorectal tubular adenoma with mild/moderate dysplasia is significantly higher than in adenoma with sever dysplasia(P<0.05). But the difference between the expression of IGFBP-4 in sporadic colorectal tubular adenoma with mild dysplasia and moderate dysplasia has not statistical significance(P>0.05).1.2 The expression of Wnt, ?-catenin, Frizzled8, CDK2 and Cyclin B1 in the process of colorectal adenoma carcinomatous1.2.1 The expression of Wnt in the process of colorectal adenoma carcinomatousImmunohistochemical results showed that the positive expression rate gradually increased in the normal colorectal mucosa, tubular adenoma with varying degrees dysplasia, and the colorectal carcinoma changed from tubular adenoma(18.2%, 51.0%, 78.0%, P<0.05). The expression of Wnt in tubular adenoma with varying degrees dysplasia and the colorectal carcinoma is significantly higher than that in the other group(P<0.05). The expression of Wnt in colorectal carcinoma is higher than that in the tubular adenoma(P<0.05). The positive expression rate gradually increased in tubular adenoma with varying degrees dysplasia(38.7%, 45.7%, 70.0%, P<0.05). The expression of Wnt in sporadic colorectal tubular adenoma with sever dysplasia is significantly higher than in the adenoma with mild/ moderate dysplasia(P<0.05). But the difference between the expression of Wnt in sporadic colorectal tubular adenoma with mild dysplasia and moderate dysplasia has not statistical significance(P>0.05).1.2.2 The expression of ?-catenin in the process of colorectal adenoma carcinomatousImmunohistochemical results showed that the abnormal expression rate gradually increased in the normal colorectal mucosa, tubular adenoma with varying degrees dysplasia, and the colorectal carcinoma changed from tubular adenoma(0.00%, 33.3%, 81.7%, P<0.05). The expression of ?-catenin in tubular adenoma with varying degrees dysplasia and the colorectal carcinoma is significantly higher than that in the other group(P<0.05). The expression of ?-catenin in colorectal carcinoma is higher than that in the tubular adenoma(P<0.05). The abnormal expression rate gradually increased in tubular adenoma with varying degrees dysplasia(12.9%, 28.6%, 60.0%, P<0.05). The expression of ?-catenin in sporadic colorectal tubular adenoma with sever/moderate dysplasia is significantly higher than in the adenoma with mild dysplasia(P<0.05). But the difference between the expression of ?-catenin in sporadic colorectal tubular adenoma with mild dysplasia and the moderate dysplasia has not statistical significance(P>0.05).1.2.3 The expression of Frizzled8 in the process of colorectal adenoma carcinomatousImmunohistochemical results showed that the positive expression rate gradually increased in normal colorectal mucosa, tubular adenoma with varying degrees dysplasia, and the colorectal carcinoma changed from tubular adenoma(42.4%, 59.4%, 81.7%, P<0.05). The expression of Frizzled8 in colorectal carcinoma is significantly higher than that in the other groups(P<0.05). But the difference between the expression of Frizzled8 in tubular adenoma with varying degrees dysplasia and normal colorectal mucosa has not statistical significance(P>0.05). The positive expression rate gradually increased in tubular adenoma with varying degrees dysplasia(45.2%, 54.3%, 80.0%, P<0.05). The expression of Frizzled8 in sporadic colorectal tubular adenoma with sever/moderate dysplasia is significantly higher than in adenoma with mild dysplasia(P<0.05). But the difference between the expression of Frizzled8 in sporadic colorectal tubular adenoma with mild dysplasia and moderate dysplasia has not statistical significance(P>0.05).1.2.4 The expression of CDK2 in the process of colorectal adenoma carcinomatousImmunohistochemical results showed that the positive expression rate gradually increased in normal colorectal mucosa, tubular adenoma with varying degrees dysplasia, and colorectal carcinoma changed from tubular adenoma(15.2%, 43.8%, 70.7%, P<0.05). The expression of CDK2 in tubular adenoma with varying degrees dysplasia and the colorectal carcinoma is significantly higher than that in the other group(P<0.05). The expression of CDK2 in colorectal carcinoma is higher than that in tubular adenoma(P<0.05). The positive expression rate gradually increased in tubular adenoma with varying degrees dysplasia(16.1%, 45.7%, 70.0%, P<0.05). The expression of CDK2 in sporadic colorectal tubular adenoma with sever/moderate dysplasia is significantly higher than that in adenoma with mild dysplasia(P<0.05). The expression of CDK2 in sporadic colorectal tubular adenoma with moderate dysplasia is significantly higher than that in adenoma with mild dysplasia(P<0.05).1.2.5 The expression of Cyclin B1 in the process of colorectal adenoma carcinomatousImmunohistochemical results showed that the positive expression rate gradually increased in normal colorectal mucosa, tubular adenoma with varying degrees dysplasia, and colorectal carcinoma changed from tubular adenoma(15.2%, 36.5%, 76.8%, P<0.05). The expression of Cyclin B1 in tubular adenoma with varying degrees dysplasia and colorectal carcinoma is significantly higher than that in the other group(P<0.05). The expression of Cyclin B1 in colorectal carcinoma is higher than that in tubular adenoma(P<0.05). The positive expression rate gradually increased in tubular adenoma with varying degrees dysplasia(16.1%, 28.6%, 66.7%, P<0.05). The expression of Cyclin B1 in sporadic colorectal tubular adenoma with moderate/sever dysplasia is significantly higher than in adenoma with mild dysplasia(P<0.05). But the difference between the expression of Frizzled8 in sporadic colorectal tubular adenoma with mild dysplasia and the moderate dysplasia has not statistical significance(P>0.05).2 Relationship between the expression of IGFBP-4 and Wnt pathways related proteins(Wnt, ?-catenin, Frizzled8, CDK2, and Cyclin B1) with clinical pathological characteristics2.1 Relationship between the expression of IGFBP-4 and clinical pathological characteristicsIGFBP-4 protein positive expression rate in colorectal carcinoma is closely related with tumor differentiation degree. IGFBP-4 protein positive expression rate decreases with the reduction of tumor differentiation degree(?~2=19.748,P<0.05) And has nothing to do with patient age, sex, lymph node metastasis, Ducks stages and infiltration depth(P>0.05)2.2 Relationship between the expression of Wnt, ?-catenin, Frizzled8, CDK2, Cyclin B1 and clinical pathological characteristics2.2.1 Relationship between the expression of Wnt and clinical pathological characteristicsWnt protein positive expression rate in colorectal carcinoma is closely related with tumor differentiation degree, Ducks stages and infiltration depth. Wnt protein positive expression rate increase with the reduction of tumor differentiation degree and the increase of Ducks stages and infiltration depth(?~2=6.186??~2=6.212,?~2=8.594,P<0.05). And it is irrelated with patients age, sex, lymph node metastasis(P>0.05).2.2.2 Relationship between the expression of ?-catenin and clinical pathological characteristicsB-catenin protein abnormal expression rate in colorectal carcinoma is closely related with tumor differentiation degree, infiltration depth and lymph node metastasis. B-catenin protein positive expression rate increase with the reduction of tumor differentiation degree and the increase of infiltration depth and lymph node metastasis(?~2=11.510,?~2=7.602,?~2=4.316, P<0.05). And it is irrelated with patients age, sex, Ducks stages(P>0.05).2.2.3 Relationship between the expression of Frizzled8 and clinical pathological characteristicsFrizzled8 protein positive expression rate in colorectal carcinoma is closely related with tumor differentiation degree. Frizzled8 protein positive expression rate increase with the reduction of tumor differentiation degree(?~2=7.228,P<0.05). And it is irrelated with patient age, sex, Ducks stages, infiltration depth and lymph node metastasis(P>0.05).2.2.4 Relationship between the expression of CDK2 and clinical pathological characteristicsCDK2 protein positive expression rate in colorectal carcinoma is closely related with tumor differentiation degree, Ducks stages and infiltration depth. CDK2 protein positive expression rate increase with the reduction of tumor differentiation degree and the increase of Ducks stages and infiltration depth(?~2=11.666,?~2=5.637, ?~2=7.599, P<0.05). And it is irrelated with patients age, sex, and lymph node metastasis(P>0.05).2.2.5 Relationship between the expression of Cyclin B1 and clinical pathological characteristicsCyclin B1 protein positive expression rate in colorectal carcinoma is closely related with tumor differentiation degree, Ducks stages and lymph node metastasis. Cyclin B1 protein positive expression rate increase with the reduction of tumor differentiation degree and the increase of Ducks stages and lymph node metastasis(?~2=9.591,?~2=4.848,?~2=6.696, P <0.05). And it is irrelated with patients age, sex, and infiltration depth(P>0.05).3 The relationship between IGFBP-4 and Wnt, ?-catenin, Frizzled8, CDK2, Cyclin B1 protein expression in the cacinogenesis of sporadic colorectal tubular adenomaResults showed that there is negative correlation between IGFBP-4 and ?-catenin, CDK2, Cyclin B1 in tubular adenoma(r=-0.209,r=-0.234,r=-0.282, P<0.05). There is a no correlation between IGFBP-4 and Wnt, Frizzled8 in tubular adenoma(P>0.05). Results showed that there is a negative correlation between IGFBP-4 and ?-catenin, CDK2, Cyclin B1 in colorectal carcinoma(r=-0.268,r=-0.310,r=-0.272, P<0.05). There is a no correlation between IGFBP-4 and Wnt, Frizzled8 in colorectal carcinoma(P>0.05).Conclusion:1 The positive expression rate of IGFBP-4 gradually decreased in normal colorectal mucosa, tubular adenoma with varying degrees dysplasia and colorectal carcinoma changed from tubular adenoma which indicates that IGFBP-4 may participate in the progress of sporadic colorectal tubular adenoma canceration and IGFBP-4 protein positive expression rate in tubular adenoma canceration is closely related with tumor differentiation degree.2 The positive expression rate of Wnt/?-catenin signaling pathway related factors(Wnt, ?-catenin, Frizzled8, CDK2 and Cyclin B1) gradually decreased in normal colorectal mucosa, tubular adenoma with varying degrees dysplasia and colorectal carcinoma changed from tubular adenoma.3 Results showed that there is a negative correlation between IGFBP-4 and Wnt/?-catenin pathway related factors which indicates that IGFBP-4 may play a role through Wnt/?-catenin in the carcinogenesis of sporadic colorectal tubular adenoma. |
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