Vasei Mohammad, Modjtahedi Helmout, Ale-Booyeh Oreineb, Mosallaei Ahmad, Kajbafzadeh Abdol Mohammad, Shahriari Mehdi, Ghaderi Abbas Ali, Soleymanpour Hossein, Kosari Farid, Moch Holger, Sauter Guido
Department of Pathology, Shiraz Medical School and Shiraz Institute of Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran.
Cancer Genet Cytogenet. 2009 Oct 15;194(2):88-95. doi: 10.1016/j.cancergencyto.2009.06.003.
Wilms tumor is one of the most common solid tumors in children. We evaluated expression and amplification of a number of genes and their prognostic significance in 45 patients with Wilms tumor, using tissue microarray technology. The expression of EGFR, ERBB2, MDM2, CCND1, MLH1, MSH2, TP53, and ABCB1 (alias MDR1) was studied by immunohistochemistry. Amplification of the EGFR, ERBB2, MDM2, CCND1, CTTN (previously EMS1), RAF1, MYC, FGF3 (previously INT2), WNT1, GLI1, CDK4, and NCOA3 (alias AIB1) genes was assessed by fluorescence in situ hybridization. Expression of EGFR was seen in 17 of the 45 cases (38%) but was not associated with gene amplification. The ERBB2 gene was neither overexpressed nor amplified in any case. Tissue microarray and immunohistochemistry analyses for ERBB2 in whole-tumor sections were also negative in all cases. Strong p53 reactivity was noted in blastemal cells in two cases with an unfavorable outcome. ABCB1 reactivity was seen in five cases with favorable histology and outcome. Only one case showed nuclear cyclin D1 positivity. All tumors showed MLH1 and MSH2 expression. All examined genes showed normal copy numbers. Unfavorable histology correlated with poor prognosis (P=0.03). There was no significant association between gene expression and prognosis. Overexpression of the EGFR gene in many Wilms tumor cases warrants further study to determine the therapeutic benefit of EGFR inhibitors in combination with other therapies in Wilms tumor patients.
肾母细胞瘤是儿童最常见的实体瘤之一。我们采用组织芯片技术评估了45例肾母细胞瘤患者中多个基因的表达、扩增情况及其预后意义。通过免疫组化研究了表皮生长因子受体（EGFR）、表皮生长因子受体2（ERBB2）、鼠双微体2（MDM2）、细胞周期蛋白D1（CCND1）、错配修复蛋白1（MLH1）、错配修复蛋白2（MSH2）、肿瘤蛋白p53（TP53）和ATP结合盒转运蛋白B1（ABCB1，别名多药耐药蛋白1，MDR1）的表达。通过荧光原位杂交评估EGFR、ERBB2、MDM2、CCND1、桩蛋白（CTTN，以前称为表皮膜蛋白1，EMS1）、丝裂原活化蛋白激酶激酶激酶1（RAF1）、原癌基因c-Myc（MYC）、成纤维细胞生长因子3（FGF3，以前称为INT2）、无翅型MMTV整合位点家族成员1（WNT1）、胶质瘤相关癌基因家族锌指蛋白1（GLI1）、细胞周期蛋白依赖性激酶4（CDK4）和核受体共激活因子3（NCOA3，别名类固醇受体辅激活因子1，AIB1）基因的扩增情况。45例中有17例（38%）可见EGFR表达，但与基因扩增无关。ERBB2基因在任何病例中均未过度表达或扩增。全肿瘤切片中ERBB2的组织芯片和免疫组化分析在所有病例中也均为阴性。在2例预后不良的病例中，胚基细胞中可见强烈的p53反应性。在5例组织学和预后良好的病例中可见ABCB1反应性。仅1例显示核细胞周期蛋白D1阳性。所有肿瘤均显示MLH1和MSH2表达。所有检测基因的拷贝数均正常。组织学不良与预后不良相关（P=0.03）。基因表达与预后之间无显著关联。许多肾母细胞瘤病例中EGFR基因的过度表达值得进一步研究，以确定EGFR抑制剂与其他疗法联合应用于肾母细胞瘤患者的治疗益处。
