PTCH1基因突变对牙源性角化囊性瘤上皮细胞增殖的影响

Effects of PTCH1 mutations on the epithelial proliferation derived from keratocystic odontogenic tumour

目的:研究牙源性角化囊性瘤(keratocystic odontogenic tumour,KCOT)中PTCH1基因突变与上皮细胞中bcl-2、丝聚合蛋白和兜甲蛋白表达的关系,探讨PTCH1基因突变对肿瘤上皮细胞增殖、分化的影响。方法:采用PCR直接测序法筛选出有PTCH1基因突变的KCOT患者及无突变者各20例,用免疫组织化学方法检测上皮细胞增殖相关蛋白bcl-2、丝聚合蛋白、兜甲蛋白在KCOT上皮细胞中的表达情况。结果:20例PTCH1基因发生突变的KCOT患者中,bcl-2强阳性12例(12/20,60%)、中度阳性4例(4/20,20%)、弱阳性4例(4/20,20%),非突变组中强阳性4例(4/20,20%)、弱阳性10例(10/20,50%)、阴性6例(6/20,30%),两组之间差异有统计学意义(U=72,P=0.001)。丝聚合蛋白表达于上皮浅层1~4层细胞,突变组中丝聚合蛋白表达弱阳性11例(11/20,55%)、阴性9例(9/20,45%),未见强阳性和中度阳性表达,非突变组中丝聚合蛋白表达中度阳性6例(6/20,30%)、弱阳性8例(8/20,40%)、阴性6例(6/20,30%),无强阳性表达病例,两组之间差异无统计学意义(U=182,P=0.48)。兜甲蛋白在突变组和非突变组KCOT衬里上皮细胞全层均呈阳性表达,两组差异无统计学意义。结论:PTCH1基因突变与KCOT肿瘤上皮细胞中bcl-2蛋白的表达水平相关,提示PTCH1基因突变可能促进肿瘤上皮细胞的增殖和分化。

Objective: To explore the relationship between the PTCH1 mutation and the expression of bcl-2,filaggrin,and loricrin in the keratocystic odontogenic tumour( KCOT),as well as the effects of the mutated PTCH1 on the epithelial proliferation and differentiation. Methods: The samples were collected from 20 cases of KCOT with mutated PTCH1,as well as 20 cases without mutation. All the samples were analyzed with immunohistochemical staining,for the purpose of investigating the expression of bcl-2,filaggrin,and loricrin. Results: In the samples with mutated PTCH1,the epithelia of 60%( 12/20) cases expressed intensively positive bcl-2 staining,20%( 4/20) expressed moderate staining,and20%( 4/20) weak staining,but no negative bcl-2 staining samples were investigated; it was significantly different from the samples without PTCH1 mutation,in which 20%( 4/20) expressed intensive staining,no moderate staining,50%( 10/20) weak staining,and 30%( 6/20) negative staining were investigated( U = 72,P = 0. 001). For the expression of filaggrin,55%( 11/20) of samples with PTCH1 mutations were stained weakly and 45%( 9/20) showed negative staining,while in the samples not harboring PTCH1 mutations,30%( 6/20) cases showed moderate positive staining,40%( 8/20) weak staining and 30%( 6/20) negative staining,no intensive staining was investigated( U = 182,P = 0. 48). The loricrin expressed in all the layer of the epithelia in all the samples,while the filaggrin was mainly localized within 1-4 layer cells of the epithelia. The differences of the expression of filaggrin and loricrin between the samples with mutated PTCH1 and without mutated PTCH1 displayed no significance. Conclusion: In the epithelia of KCOT,the bcl-2 expression was significantly associated with the PTCH1 mutation,which suggested that the mutated PTCH1 gene perhaps promotes the proliferation of KCOT epithelium.