Wnt1信号通路蛋白分子在肾上腺及神经母细胞瘤组织中表达的研究

目的 观察新生儿肾上腺、>2岁小儿肾上腺和神经母细胞瘤组织中经典Wnt信号通路中Wnt1、β-catenin和CyclinD1的表达,探讨Wnt1信号通路调控异常与神经母细胞瘤的相关性.方法 应用免疫组化方法 检测新生儿肾上腺、>2岁小儿肾上腺及各期、各病理类型、化疗前后神经母细胞瘤组织中Wnt1信号通路中Wnt1、β-catenin和CycinD1的表达.结果术前未化疗的肿瘤Wnt1和β-catenin蛋白表达明显强于新生儿肾上腺组织,后者又明显强于>2岁小儿肾上腺(P=0.014),差别均具有高度的统计学意义;Ⅲ～Ⅳ期肿瘤的Wnt1和β-catenin蛋白表达较Ⅰ～Ⅱ期肿瘤高;Ⅲ～Ⅳ期肿瘤中术前未化疗的Wnt1和β-catenin蛋白表达明显高于术前化疗的肿瘤;组织预后不良型(UH)肿瘤Wnt1和β-catenin蛋白表达较组织预后良好型(FH)肿瘤高,差别具有高度的统计学意义.新生儿肾上腺及>2岁小儿肾上腺组织中CyclinD1染色均为阴性,而肿瘤组织中表达阳性,Ⅰ～Ⅱ期肿瘤与Ⅲ～Ⅳ期术前未化疗的肿瘤CyclinD1蛋白表达无差别;Ⅲ～Ⅳ期术前未化疗的肿瘤CyclinD1蛋白表达明显高于术前化疗的肿瘤,UH肿瘤的CyclinD1蛋白表达高于FH肿瘤.结论 Wnt1信号通路对肾上腺细胞分化成熟有一定的调控作用.Wnt1通路异常可能是参与神经母细胞瘤发生和侵袭的重要机制.

The role of Wnt1 signaling pathway in the oncogenic transformation and invasion of neuroblastomas

Objective To investigate the role of Wnt1 signaling pathway in the oncogenic trans-formation and invasion of neuroblastomas. Methods Immunohistochemical staining was performed to examine the expressions of Wnt1 signaling proteins including Wnt1,β-catenin and CyclinD1 in adrenal glands and neuroblastoma tissues. Results In the patients without preoperative chemotherapy,the ex-pressions of Wnt1 and β-catenin in neuroblastoma tissues were significantly higher than those of neo-natal adrenal glands. The expressions of Wnt1 and β-catenin in stage Ill-IV neuroblastoma were signif-icantly higher than those of stage Ⅰ-Ⅱ. For tumors of stage Ⅲ-Ⅳ,Wnt1 and β-catenin expressions were significantly decreased in preoperative chemotherapy subgroup than that of non-preoperative chemotherapy subgroup. Wnt1 and β-catenin of unfavorable histology (UH) neuroblastoma were significantly higher than those of favorable histology (FH). In adrenal glands of the neonates,Wnt1 and β-catenin expressed significantly higher than those of the patients older than 2 years of age. The expression of CyclinD1 was negative in the adrenal glands of neonates and patients older than 2 years of age; but it was positive in neuroblastoma tissues. In the patients without preoperative chemotherapy,no difference of CyclinD1 expression was found between stage Ⅰ-Ⅱ and stage Ⅲ-Ⅳ. For tumors of stage Ⅲ-Ⅳ,the CyclinD1 expression was significantly decreased in preoperative chemotherapy subgroup than that of non-preoperative chemotherapy subgroup. The expression of CyclinD1 of UH neuroblastoma was significantly higher than that of FH neuroblastoma. Conclusions Wnt1 signaling pathway plays a role in regulating adrenal gland maturity. The dysregulated Wnt1 signaling may contribute to the oncogenic transformation and invasion of neuroblastoma.