视网膜母细胞瘤组织芯片中PTEN、mdm2、p53表达及与组织病理特征关系的研究

Detection of PTEN, mdm2 and p53 expression in retinoblastoma tissue microarrays and their relationship with clinical and histopathological characteristics

目的探讨视网膜母细胞瘤组织芯片中PTEN,murine double minute 2(mdm2)及p53蛋白的表达及与肿瘤临床组织病理特征的关系。设计实验性研究。研究对象64例视网膜母细胞瘤和6例正常视网膜组织。方法免疫组化方法检测视网膜母细胞瘤组织芯片和正常视网膜组织石蜡标本中PTEN,mdm2及p53的表达情况,将肿瘤分为球后视神经受侵袭组和球后视神经未受侵组,检测两组间mdm2及p53表达差异,并结合肿瘤的组织病理学特征进行综合分析。主要指标视网膜母细胞瘤组织芯片中PTEN,mdm2和p53表达率。结果视网膜母细胞瘤中PTEN,mdm2与p53的阳性表达率分别为53.13%,48.43%和53.13%。球后视神经受侵袭组较球后视神经未受侵组mdm2(P=0.027)及p53(P=0.017)表达均明显增高。视网膜母细胞瘤中PTEN与p53表达呈负相关(r=-0.384,P=0.045),mdm2与p53蛋白表达呈正相关(r=0.28l,P=O.018)。结论视网膜母细胞瘤中mdm2和p53的过度表达与视神经侵袭程度存在一定相关性。mdm2及p53蛋白的检测可能成为视网膜母细胞瘤恶性程度的参考指标。

Objective To investigate the expression of PTEN, murine double minute 2 （mdm2）and p53 protein in retinoblastoma （Rb） cells with tissue microarrays and to evaluate their relationship with clinical and histopathoological characteristics. Design Experimental study. Participants Sixty-four cases of Rb and 6 cases of normal retina. Methods Tissue microarrays and normal retinal tissues were used to determine the expression of PTEN, mdm2 and p53 with SP immunochemical method. The relationship between those protein expression and clinical parameters were analyzed. Main Outcome Measures Positive expression rate of PTEN, mdm2 and p53. Results The positive expression of PTEN, mdm2 and p53 were 53.13%, 48.43% and 53.13%. The optic nerve infiltrated group of Rb significantly expressed mdm2 （P=0.027） and p53 （P=0.017） compared with the optic nerve non-infihrated group. The expression of p53 were significantly associated with PTEN （r=-0.384, P=-0.045） and mdm2 （r=0.281, P=-0.018）. Conclusions Mdm2 and p53 are significantly associated with the infiltration of retinoblastoma. The overexpression of mdm2 and p53 lead to the loss of cell cycle control and may contribute to tumorgenesis and tumor progress in retinoblastoma. Mdm2 and p53 may be regarded as prognostic indicators and new targets for chemotherapy of Rb.