p16和bcl-2基因在膀胱癌中的表达及意义

p16 Tumor Suppressor Gene and bcl-2 Gene in Bladder Transitional Cell Carcinoma and their Significance

[目的]探讨p16抑癌基因和bcl 2凋亡抑制基因与膀胱癌生物学行为的关系。[方法]采用免疫组化和核酸原位杂交等方法检测67例膀胱癌中p16和bcl 2基因的表达。[结果]67例膀胱癌p16蛋白表达阳性率52 23 %(35/67) ,失表达率47 76 %(32/67) ,其中Ⅰ级、Ⅱ级、Ⅲ级的肿瘤p16蛋白失表达率各为14 55%、60 53 %、71 43 %(P<0 05) ;p16mRNA失表达率分别为20%、40 %、80 %(P<0 05)。而bcl 2蛋白表达阳性率59 70 %(40/67) ,分别为Ⅰ级36 36 %、Ⅱ级65 79 %、Ⅲ级100% ,bcl 2mRNA阳性表达率各为40%、60 %、100 %(P<0 05)。免疫组化和原位杂交结果一致(P>0 05)。[结论]p16基因表达与细胞分化呈负相关 ,bcl 2基因表达与细胞分化呈正相关 ,提示 p16基因的缺失、突变和高甲基化 ,bcl 2基因的异常表达在膀胱癌的发生和发展中起重要的推动作用 。

To evaluate the relationship between alterations of p16 tumor suppressor gene,bcl 2 apoptosis suppressor gene,and the biological behaviors of bladder transitional cell carcinoma (BTCC).Sixty_seven cases with BTCC were examined for p16 and bcl 2 protein expression with immunohistochemical staining.Twenty cases of BTCC were examined for p16 and bcl 2 mRNA expression with nucleic acid hybridization in situ.The positive rate of p16 protein expression was 52 23%(35/67) in BTCC.The rate in grade Ⅰ,Ⅱ and Ⅲ were 14 55%,60 53%and 71 43%(P<0 05), and their negative rate of mRNA expression were 20%,40%and 80%(P<0 05) respectively.The total positive rate of bcl 2 protein expression was 59 70%(40/67),grade Ⅰ,Ⅱ and Ⅲ were 36 36%,65 79%and 100%(P<0 05),and their positive rate of mRNA expression were 40%,60% and 100% (P<0 05)respectively.The results of hybridization in situ were highly concident with immunohistochemical staining (P<0 05).[Conclusion]p16 gene expression is negative correlated with cell differentiation,while bcl 2 gene expression is positive correlated.It is shown that deletion,mutation and hypermethylation of p16 gene and abnormal expression of bcl 2 gene are important in enhancing the development of BTCC and both p16 gene and bcl 2 gene may be used as markers for evaluating biological behavior of BTCC.