Clinicopathological Significance Of The Expression Of CDC25A,p57^Kip2,CDK2 And CyclinE In Colorectal Carcinoma

Objective: To study the clinicopathological significance of the expression of CDC25A,p57^Kip2,CDK2 and cyclinE in colorectal carcinoma. To investigate the correlation of the expression of CDC25A,p57^Kip2,CDK2 and cyclinE with clinical pathological characteristics in colorectal carcinoma.To investigate the corelation between CDC25A,p57^Kip2,CDK2 and cyclinE. Provide abnormality of many genes involved the regulatory pathway of CDC25A,p57^Kip2,CDK2 and cyclinE in the molocular mechanism of colorectal carcinogenesis.Methods: Immunohistochemical technique SP was used to examine the expression of CDC25A,p57^Kip2,CDK2 and cyclinE in 45 cases of colorectal carcinomas and their surrounding tissues (3cm distanced)and (10cm distanced) normal tissues. The levels the expression were analyzed combined with clinicopathological features of the patients including age, the cases, tumor size, loci of the tumor, infiltration depth, differentiation degree, histology type, lymph node metastasis, and Dukes-stages.Results: Buffy color staining found in cytoplasms and/or nucleus was recognized as positive. CDC25A located in nucleus. p57^Kip2, CDK2 and cyclinE located in nucleus and cytoplasm.Overexpression of CDC25A revealed in 39/45 samples(86.7%)of carcinoma which showed a negative correlation with tumor differentiation. The expression of CDC25A was lower in high and moderate differentiation degree than those in poor differentiation degree and the rate of positive expression was 76.0%(19/25)and 100.0%(20/20)respectively (P<0.05). The expression percent of CDC25A was 100.0%(17/17)in lymph node metastatic cancer whereas only 78.6%(22/28)of CDC25A expression were shown in non-metastatic cancer(P<0.05). The positive expression percents of CDC25A in distant metastatic cancer and nondistant metastatic cancer were 92.9%(13/14)and 83.9%(26/31)respectively(P>0.05). The expression of CDC25A in A+B Dukes-stages was significantly lower than that in C+D Dukes-stages and the rate of positive expression was 78.6%(22/28)and 100.0%(17/17)respectively(P<0.05). The over expression rate of CDC25A in cancer tissues were significantly higher than that in tumor-adjacent and normal colorectal carcinoma tissues(P<0.01,P<0.01).The expression of CDC25A was 51.1%(23/45)in the surrounding tissues of 3cm distance which showed significantly higher than that in normal tissues and the rate of positive expression was 20.0%(9/45)(P<0.01). Lowerxpression of p57^Kip2 revealed in 18/45 samples(40.4%)of carcinoma which showed a positive correlation with tumor differentiation. The expression of p57^Kip2 was higher in high and moderate differentiation degree than those in poor differentiation degree and the rate of positive expression was 56.0%(14/25)and 20.0%(4/20)respectively (P<0.05). The expression percent of p57^Kip2 was 29.4%(5/17)in lymph node metastatic cancer whereas only 46.4%(13/28)of p57^Kip2 expression were shown in non-metastatic cance(rP>0.05). The positive expression percents of p57^Kip2 in distant metastatic cancer and nondistant metastatic cancer were 14.3%(2/14)and 51.6%(16/31)respectively(P>0.05). The expression of p57^Kip2 in A+B Dukes-stages was significantly higher than that in C+D Dukes-stages and the rate of positive expression was 53.6%(15/28)and 17.6%(3/17)respectively(P<0.05). The expression rate of p57^Kip2 in cancer tissues40.0%(18/45) was not significantly lower than that in tumor-adjacent tissues51.1%(23/45)(P>0.05). The expression rate of p57^Kip2 in cancer tissues and tumor-adjacent tissues were significantly lower than that in normal tissues 73.3%(34/45)(P<0.01,P<0.05). Overexpression of CDK2 revealed in 26/45 samples(57.8%)of carcinoma which showed a negative correlation with tumor differentiation. The expression of CDK2 was lower in high and moderate differentiation degree than those in poor differentiation degree and the rate of positive expression was 48.0%(12/25)and 90.0%(18/20)respectively (P<0.01). The expression percent of CDK2 was 88.2%(15/17)in lymph node metastatic cancer whereas only 39.3%(11/28)of CDK2 expression were shown in non-metastatic cancer(P<0.01). The positive expression percents of CDK2 in distant metastatic cancer and nondistant metastatic cancer were 92.9%(13/14)and 41.9%(13/31)respectively(P<0.01). The expression of CDK2 in A+B Dukes-stages was significantly lower than that in C+D Dukes-stages and the rate of positive expression was 42.9%(12/28)and 82.4%(14/17)respectively(P<0.01). The over expression rate of CDK2 in cancer tissues 57.8%(26/45)were significantly higher than that in tumor-adjacent and normal colorectal carcinoma tissue(sP<0.05,P<0.01). The expression rate of CDK2 in tumor-adjacent cancer tissues 35.6%(16/45)was significantly higher than that in normal colorectal carcinoma tissues 11.1%(5/45)(P<0.01). Overexpression of cyclinE revealed in 28/45 samples(62.2%)of carcinoma which showed a negative correlation with tumor differentiation. The expression of cyclinE was lower in high and moderate differentiation degree than those in poor differentiation degree and the rate of positive expression was 48.0%(12/25)and 80.0%(16/20)respectively (P<0.05). The expression percent of cyclinE was 88.2%(15/17)in lymph node metastatic cancer whereas only 46.4%(13/28)of cyclinE expression were shown in non-metastatic cancer(P<0.01). The positive expression percents of cyclinE in distant metastatic cancer and nondistant metastatic cancer were 85.7%(12/14)and 51.6%(16/31)respectively(P<0.05). The expression of cyclinE in A+B Dukes-stages was significantly lower than that in C+D Dukes-stages and the rate of positive expression was 46.4%(13/28)and 88.2%(15/17)respectively(P<0.01). The over expression rate of cyclinE in cancer tissues 62.2%(28/45)were significantly higher than that in tumor-adjacent and normal colorectal carcinoma tissue(sP<0.01,P<0.01). The expression rate of cyclinE in tumor-adjacent cancer tissues 22.2%(10/45)was not significantly higher than that in normal colorectal carcinoma tissues 8.9%(4/45)(P>0.05). There were no significant differences in the age and sex of the cases, the size and loci of the tumor of the expression of CDC25A, p57^Kip2, CDK2 and cyclinE(P>0.05). There is a negative relationship between CDC25A and p57^Kip2 , p57^Kip2 and CDK2 , p57^Kip2 and cyclinE(P<0.01). There is a positive relationship between CDC25A and CDK2, CDC25A and cyclinE, CDK2 and cyclinE(P<0.01).Conclusion: Over expression of CDC25A, CDK2 and cyclinE exsist in colorectal carcinoma and show a good relation with tumor differentiation and Dukes-stages. Lower expression of p57^Kip2 in colorectal carcinoma and show a good relative with tumor differentiation and Dukes-stages. CDC25A expression maybe regulated by CDK2 and cyclinE. Both the over expression of CDC25A and the lower expression of p57^Kip2 coexist in the development of colorectal carcinoma. Abnormality of many genes involved in the regulatory pathway of CDC25A, p57^Kip2, CDK2 and cyclinE maybe involved in the molocular mechanism of colorectal carcinogenesis.