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目的探讨Bcl-2基因与细胞凋亡的相关性及在儿童骨肉瘤发生发展中的作用及临床意义。方法选取1998年1月—2010年3月泰山医学院附属医院、泰安市妇幼保健院收治并确诊的儿童骨肉瘤病例41例,均石蜡病理确诊,将接受规范治疗的患儿(包括手术及术前术后的化疗)纳入本组研究范围,共计36例应用免疫组织化学法对36例儿童骨肉瘤组织,20例骨软骨瘤组织中Bcl-2的表达水平进行检测。单因素分析Bcl-2与患儿性别、年龄、原发肿瘤部位、肿瘤直径、病理分型、Enneking分期的相关性。采用DNA末端原位标记法(TUNEL法)检测儿童骨肉瘤及软骨瘤组织中的细胞凋亡,计算凋亡指数(AI)后分析与Survivin及Bcl-2表达的相关性,并对其临床意义进行初步探讨。结果 Bcl-2表达:36例儿童骨肉瘤组织中Bcl-2表达阳性率为47.2%(17/36),对照组20例骨软骨瘤组织中未见表达(P<0.05);Bcl-2阳性表达与性别、年龄、肿瘤部位、肿瘤直径、病理分型无明显相关,与Enneking外科分期及相关,EnnekingI～II期阳性率为30%(6/20),III期阳性率为62.5%(10/16),差异有统计学意义(P<0.05)。说明分期越高,Bcl-2表达越显著。AI范围3.6%～16.4%,均值7.3%,经检验在儿童骨肉瘤组织中细胞AI为(6.66±1.87)%,对照组组为(12.28±3.29)%,两组间差异有统计学意义(P<0.05),说明骨肉瘤中的细胞凋亡减少。AI在Bcl-2阳性组为(4.68±0.57)%和阴性组(6.53±1.65)%两组间差异有显著性(P<0.05)。Bcl-2的表达与AI呈负相关。采用Kaplan-Meier法绘制Bcl-2阳性组和阴性组生存曲线,提示Bcl-2阳性组生存期显著低于阴性表达者。Cox回归模型进行多因素生存分析显示,骨肉瘤的Enneking分期,Bcl-2的表达水平是儿童骨肉瘤预后相关的独立的重要因素。结论 Bcl-2在儿童骨肉瘤中阳性表达与性别、年龄、肿瘤部位、肿瘤直径、病理分型无明显相关,与Enneking分期相关。Bcl-2的阳性表达缩短骨肉瘤患儿的生存时间。Bcl-2的表达均与AI呈负相关。说明Survivin、Bcl-2蛋白可能阻碍了儿童骨肉瘤细胞的凋亡,促进了肿瘤的分裂增殖。多因素分析显示,骨肉瘤Enneking外科分期及Bcl-2的表达为骨肉瘤重要的预后因素。综合分析以上指标对判断儿童骨肉瘤预后有重要的参考价值。
Objective To investigate the correlation between Bcl-2 gene and apoptosis and its role in the development of osteosarcoma in children and its clinical significance. Methods From January 1998 to March 2010, 41 cases of pediatric osteosarcoma were admitted to Taishan Medical College Affiliated Hospital and Tai’an Maternal and Child Health Hospital, all were pathologically diagnosed with paraffin, and children undergoing standard treatment (including surgery and operation Before and after chemotherapy) into the scope of this study, a total of 36 cases of immunohistochemistry in 36 cases of osteosarcoma in children, 20 cases of osteochondroma tissue Bcl-2 expression levels were detected. Univariate analysis of Bcl-2 in children with gender, age, primary tumor site, tumor diameter, pathological type, Enneking staging relevance. The apoptosis of children with osteosarcoma and chondroma was detected by TUNEL method. The correlation between Survivin and Bcl-2 expression was analyzed after calculating the AI and the clinical significance For a preliminary discussion. Results The positive rate of Bcl-2 expression in osteosarcoma tissues was 47.2% (17/36) in 36 children and 20 cases in osteochondroma tissues in control group (P <0.05). The positive rate of Bcl-2 The positive expression rate of Enneking stage I ~ II was 30% (6/20), while the positive rate of stage III was 62.5% (10) / 16), the difference was statistically significant (P <0.05). The higher the staging, the more significant the expression of Bcl-2. AI ranged from 3.6% to 16.4% with a mean of 7.3%. The AI of the cells was (6.66 ± 1.87)% in children with osteosarcoma and (12.28 ± 3.29)% in control group, with significant difference between the two groups P <0.05), indicating reduced apoptosis in osteosarcoma. AI in the Bcl-2 positive group (4.68 ± 0.57)% and negative group (6.53 ± 1.65)% difference between the two groups was significant (P <0.05). The expression of Bcl-2 was negatively correlated with AI. Survival curve of Bcl-2 positive group and negative group was drawn by Kaplan-Meier method, which indicated that survival of Bcl-2 positive group was significantly lower than negative expression. Cox regression model of multivariate survival analysis showed that osteosarcoma Enneking staging, Bcl-2 expression levels in children with osteosarcoma prognosis-related independent important factor. Conclusion The positive expression of Bcl-2 in childhood osteosarcoma has no correlation with gender, age, tumor location, tumor diameter and pathological type, and is correlated with Enneking staging. The positive expression of Bcl-2 shorten the survival time of children with osteosarcoma. The expression of Bcl-2 was negatively correlated with AI. These results suggest that Survivin and Bcl-2 may hinder the apoptosis of osteosarcoma cells in children and promote the proliferation and proliferation of tumors. Multivariate analysis showed that the Enneking surgical stage and Bcl-2 expression in osteosarcoma were important prognostic factors of osteosarcoma. Comprehensive analysis of the above indicators for judging the prognosis of children with osteosarcoma has important reference value.