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

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

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、6-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CyclinDl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。

Objective To investigate the role of Wntl signaling pathway in the oncogenic transformation and invasion of neuroblastomas. Methods Immunohistochemical staining was performed to examine the expressions of Wntl signaling proteins including Wntl,β-catenin and CyclinD1 in adrenal glands and neuroblastoma tissues. Results In the patients without preoperative chemotherapy, the expressions of Wnt1 and β-catenin in neuroblastoma tissues were significantly higher than those of neonatal adrenal glands. The expressions of Wntl and β-catenin in stage III-IV neuroblastoma were significantly higher than those of stage I - II. For tumors of stage III-IV, Wntl 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, Wntl 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 Ill-IV, the CyclinD1 expression was significantly decreased in preoperative chemotherapy subgroup than that of non-preoperative chemotherapy subgroup. The expression of CyelinD1 of UH neuroblastoma was significantly higher than that of FH neuroblastoma. Conclusions Wntl signaling pathway plays a role in regulating adrenal gland maturity. The dysregulated Wntl signaling may contribute to the oncogenie transformation and invasion of neuroblastoma.