多发性结直肠癌中抑癌基因p53的表达与突变

Gene mutation and protein expression of p53 in multiple colorectal cancers

目的探讨抑癌基因p53与多发性结直肠癌的关系。方法实验组为同时多发性结直肠癌19个癌灶和结直肠再发癌12个癌灶,对照组为散发性结直肠癌17个癌灶。分别采用免疫组织化学抗生物素蛋白生物素过氧化物酶复合物(ABC)方法和单链DNA构像多态性(PCRSSCP)方法对癌组织和癌旁正常组织进行p53蛋白以及p53基因第5、7、8外显子突变的检测,比较各组蛋白表达和基因突变的不同。结果在同时多发癌组、再发癌组以及对照组中p53蛋白阳性表达率分别为73.7%、75%、35.3%,3组比较差异有统计学意义(χ2=6.952,P<0.05);突变率3组分别为52.6%、41.7%、29.4%,差异均无统计学意义。癌旁正常组织均未检出突变;但蛋白表达在同时性三发性癌患者中为阳性。结论多发性结直肠癌中p53基因突变率和蛋白表达高于散发性结直肠癌。p53过度表达的结直肠癌患者要警惕多发癌的发生。

Objective To study the relationship between the tumor suppressor gene p53 and multiple colorectal cancers.Methods The research group consisted of 19 synchronous colorectal caners and 12 metachronous colorectal cancers.The expression of p53 was detected by immunohistochemical staining and mutations of exons 5,7 and 8 within the p53 gene was identified by PCR-SSCP.The p53 gene mutation rate and its protein expression rate were compared with those of 17 sporadic colorectal cancers.Results The expression of p53 in synchronous group,metachronous group and sporadic group was 73.7%,75% and 35.3% respectively with the difference being significant (χ2=6.952,P=0.031),while the p53 gene mutation rate was 52.6% (10/19),41.7% (5/12),29.4% (5/17) respectively with no statistical difference.Seven of the 9 patients were identified with p53 gene mutation in synchronous group,which was significantly higher than those in sporadic group (χ2=5.539,P=0.038).No p53 gene mutation was detected in adjacent normal mucous,but the patient with 3 synchronous cancers had p53 protein expression in adjacent normal mucous.Conclusion Rate of p53 gene mutation and its protein expression is higher in multiple colorectal cancers than those in sporadic colorectal cancer.Colorectal cancer patients with over-expression of p53 protein may easily have got multiple colorectal cancers.