Notch1和Notch2在星形细胞瘤及髓母细胞瘤中的表达及其意义

Differential expression of Notch1 and Notch2 in astrocytoma and medulloblastoma

目的探讨Notch1和Notch2在人脑星形细胞瘤及髓母细胞瘤中的表达及其在肿瘤形成和发展中的作用。方法应用组织芯片和免疫组织化学SP法染色以及Westernblot技术检测正常脑组织、不同级别大脑星形细胞瘤、小脑髓母细胞瘤中Notch1和Notch2蛋白的表达情况。结果正常脑组织中Notch1和Notch2蛋白呈阴性表达；Notch1在Ⅳ级星形细胞瘤中阳性比为15／15，Ⅲ级中阳性比为14／15，Ⅱ级中阳性比为10／15，Ⅰ级中阳性比为9／15，总阳性率为80．O％（48／60），阳性部位均为胞质。Ⅰ、Ⅱ、Ⅲ、Ⅳ级星形细胞瘤中表达阳性比及表达强度随肿瘤级别增高而增高。在髓母细胞瘤中阳性比为2／10，且表达水平较低。Notch2在Ⅳ级星形细胞瘤中无表达（0／15），Ⅲ级表达阳性比为1／15，Ⅱ级中阳性比为2／15，Ⅰ级中阳性比为3／15，总阳性率为10％（6／60），表达率及表达强度都很低。在髓母细胞瘤中阳性比为9／10。Notchl在各级别胶质瘤中表达强度的差异均有统计学意义（Χ^2=18．495，P〈0．05）。Spearman等级相关检验证实肿瘤病理分级与Notch1表达强度之间呈正相关（r=0．859，P〈0．05）。在星形细胞瘤中，Notch1和Notch2表达的总阳性率差异有统计学意义（Χ^2=56．807，P〈0．05），在髓母细胞瘤中，Notch1和Notch2的表达差别有统计学意义（Χ^2=13．778，P〈0．05）。结论Notch1和Notch2在星形细胞瘤及髓母细胞瘤中表达不同，并呈现相反的趋势，可能与两者在脑发育过程中的作用不同有关。

Objective To detect the differential expression of Notch1 and Notch2 in human astrocytoma and medulloblastoma; and to study the role of Notch1 and Notch2 in the development of both tumors. Methods Immunohistochemical staining （SP method） and Western blot analysis were used to detect Notch1 and Notch2 expression in tissue arrays and freshly resected samples of normal brain tissue, astrocytoma and medulloblastoma. Results Notch1 and Notch2 were negative in normal human brain tissue. Notch1 was highly expressed （total positive rate 80. 0% , 48/60） while Notch2 was not detected in grade Ⅳ astrocytomas and sporadically observed in lower grade astrocytomas （total positive rate 10. 0%, 6/60）. The percentage of positive tumor cells and expression level of Notch1 increased with higher histologic grade （r = 0. 859 ,P 〈 0. 05 ）. On the other hand, overexpression of Notch2 was detected in medulloblastoma （9/10） in contrast with lower expression of Notch1 （2/10）. Conclusions Notch1 and Notch2 show differential expression in astrocytoma and medulloblastoma. This may be related to their different functional activities during the process of brain development.