Expression And Significance Of P53,p21^WAF-1 And P63 In Gastrointestinal Stromal Tumors

Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumors in gastrointestinal tract. The incidence of GISTs moved upward year by year. It is difficult to determine the biological behavior of GISTs. It had showed that the molecular mechanism of GISTs were related to the activation of proto- oncogene and the inactivation of tumor suppressor gene. Wild-type p53 is an important tumor suppressor gene. Mutations of p53 are observed in about more than 50% of all malignant tumors in human. The negative regulation for the cells by mutant-typep53 was lost and then the tumor occurred. P21WAF-1 is a tumor suppressor gene regulated by the wile-type p53. It mainly inhibits the activity of cyclin/cdk2 complexes and negatively modulates cell cycle pro- gression. P63 is a new member of p53 family. Like p53, p63 is expressed as multiple isoforms. P63 exerts its tumor suppressor function in association with p53 within a complex network of physical and functional interactions. In our study, the expression of p53, p21WAF-1 and p63 were detected in 70 cases of GISTs by immunohistochemistry method. This study was designed to invest- tigate the relationship between the expression of p53, p21WAF-1, p63 and the clinicopathologica features of GISTs. And the study also designed to investigate the correlation of the expression of the 3 proteins in GISTs.METHODSImmunohistochemical SP method was used to detect p53, p21WAF-1 and p63 expression in 70 cases of GIST.Statistical analysisχ2 test, Fisher exact Probabilities and spearman correlation analysis were used with SPSS 11.5 soft ware. P<0.05 was considered statistically significant.RESULTS1.We divided into low-risk and middle-risk and high-risk to refer to the standard of Fletcher. The positive expression of p53 is increased and the positive expression of p21WAF-1 is redused by degrees (P<0.01).2. The positive expression of p53 is increased and the positive expression of p21WAF-1 is redused by degrees (P<0.01) in the cases which were divided into three classes according to diameter (≤5cm, 6-10cm and >10cm) and caryocinesis number (≤5/50HPF, 6-10/HPF and >10/HPF).3. We divided into two groups refer to the necrosis by degrees(P<0.05) .4. Correlation among p53, p21 WAF-1 and p63 expression in GIST.(1) Correlation between p53 and p21 WAF-1 expression . There was a negative correlation between p53 and p21 WAF-1 expression (r=-0.538, P=0.000) .(2) Correlation between p63 an p53 expression . There was no correlayion between p63 and p53 expression (r=0.145, P=0.232).(3) Correlation between p63 an p21 WAF-1 expression . There was no correlayion between p63 and p53 expression (r=0.049, P=0.686)CONCLUSION1. p53, p21WAF-1 and p63 expression is closely related with the prognosis of GIST and can be served as important preditors for survival.2. The positive expression of p53, p21WAF-1 and p63 were rated to nuclear mitosis accounts, tumor diameter and Fletcher grading. There were higher rates of p53 than that of low and intermediate GISTs. While on the contrary, the positive rate of p21WAF-1 expression was lower in high risk GISTs than that of low and intermediate GISTs. The expression of p53, p63 and p21 WAF-1 maybe potential evaluationary index to determin the biological behavior of GISTs. 3. There was a negative correlation between p53 and p21 WAF-1 expression; There were no correlation between p53 and p63 or p63 and and p21WAF-1 .