机构：[1]Capital Med Univ, Basic Med Coll, Dept Pathol, Beijing 100069, Peoples R China;[2]Capital Med Univ, Beijing Childrens Hosp, Dept Pathol, Beijing 100069, Peoples R China;医技科室病理科首都医科大学附属北京儿童医院[3]Inner Mongolia Med Coll, Dept Pathol, Hohhot, Peoples R China;[4]Capital Med Univ, Basic Med Coll, Dept Pathol, 10 Xitoutiao, Beijing 100069, Peoples R China
Background: ALK gene has been identified as a major neuroblastoma (NBL) predisposition gene. But ALK gene copy number and protein expression in ganglioneuroblastoma (GNBL) and ganglioneuroma (GN) are poorly described in the literature. Furthermore, there are controversies on the correlation between ALK protein expression and clinical outcome in NBL. Methods: We evaluated MYCN/ALK gene copy number by fluorescence in situ hybridization (FISH) and detected ALK protein expression by immunohistochemistry (IHC) in 188 NBL, 52 GNBL and 6 GN samples and analyzed their association with clinical outcome of the patients. Results: Although ALK gene copy number increase is a recurrent genetic aberration of neuroblastic tumors (NTs) (39.1%, 96/246), ALK amplification was only present in three NBLs (1.2%, 3/246). The frequency of ALK positivity in NBL (50.5%, 51/101) was significantly higher than in GNBL (22.6%, 7/31) and in GN (0.0%, 0/4) (P < 0.05). In addition, ALK positivity also significantly correlates with MYCN/ALK gene copy number increases (P < 0.05). Kaplan-Meier survival analysis indicated that MYCN/ALK amplification is correlated with decreased overall survival in NBL. A better prognosis trend was observed in patients with MYCN/ALK gain tumors compared with those with MYCN/ALK normal tumors. Furthermore, ALK positivity significantly correlated with inferior survival in NBL (P = 0.044). Conclusion: ALK positivity in NTs correlated with advanced tumor types and MYCN/ALK gene copy number increases. ALK positivity predicts inferior prognosis in NBL and IHC is a simplified strategy to screen ALK positivity in clinical practice. (c) 2013 Elsevier Inc. All rights reserved.
基金：
Natural Science Foundation of ChinaNational Natural Science Foundation of China [81001054]; Beijing Natural Science Foundation of ChinaBeijing Natural Science Foundation [7122025]; Excellent talents of Science Program, Beijing, China [2011D005018000008]; Foundation for University Key Teacher by the Ministry of Education [3500-11250609]
第一作者机构：[1]Capital Med Univ, Basic Med Coll, Dept Pathol, Beijing 100069, Peoples R China;
通讯作者：
通讯机构：[1]Capital Med Univ, Basic Med Coll, Dept Pathol, Beijing 100069, Peoples R China;[4]Capital Med Univ, Basic Med Coll, Dept Pathol, 10 Xitoutiao, Beijing 100069, Peoples R China
推荐引用方式(GB/T 7714)：
Wang Miao,Zhou Chunju,Sun Qinnuan,et al.ALK amplification and protein expression predict inferior prognosis in neuroblastomas[J].EXPERIMENTAL AND MOLECULAR PATHOLOGY.2013,95(2):124-130.doi:10.1016/j.yexmp.2013.06.002.
APA：
Wang, Miao,Zhou, Chunju,Sun, Qinnuan,Cai, Rongqin,Li, Yong...&Gong, Liping.(2013).ALK amplification and protein expression predict inferior prognosis in neuroblastomas.EXPERIMENTAL AND MOLECULAR PATHOLOGY,95,(2)
MLA：
Wang, Miao,et al."ALK amplification and protein expression predict inferior prognosis in neuroblastomas".EXPERIMENTAL AND MOLECULAR PATHOLOGY 95..2(2013):124-130
