儿童侵袭性纤维瘤中β-catenin的表达和基因突变分析及与复发相关性实验研究

Experimental study of relations of β-catenin expression and gene mutation and tumor recurrence in pediatric aggressive fibromatosis

目的分析儿童侵袭性纤维瘤病β-catenin的表达和突变状态,并探讨其与肿瘤复发的相关性。方法搜集该院2007年6月—2013年5月期间手术留取侵袭性纤维瘤标本,应用免疫组化法对32例侵袭性纤维瘤病患儿(21例复发和11原发性发病例)和15例对照组进行分析。在β-catenin的3号外显子的体细胞点突变进行聚合酶链反应产物的测序。结果在侵袭性纤维瘤病样本中检测β-catenin的核表达为94%(30/32),而对照组为13%(2/15)(P<0.001)。在侵袭性纤维瘤病样本中B连环蛋白基因3号外显子突变率为78%(25/32)(19/21复发病例,6/11原发发病例;P=0.032)。在复发病例主要发生突变的密码子是45(S45F),而原发病例中41号密码子(T41A)是最常见的突变(P=0.002)。结论在β-catenin基因中,3号外显子的改变,特别是S45F突变,可以作为儿童患者复发的危险因素和可能被用作预后因素。

Objective To analyze the expression and mutation status of β-catenin in pediatric aggressive fibromatosis and explore the relation with tumor recurrence.Method Beta-catenin expression was analyzed by immunohistochemistry in 32 samples from pediatric patients with aggressive fibromatosis （21 recurrent cases and 11 primary -onset cases）and 15 control subjects.Somatic point mutations in β-catenin exon 3 were identified by sequencing of polymerase chain reaction products.Results Nuclear expression of β-catenin was detected in 94% （30 /32）of aggressive fibromatosis samples and 13% （2 /15）of control samples （P =0.001）.Mutations in ex-on 3 of the β-catenin gene were identified in 78% （25 /32）of aggressive fibromatosis samples （19 /21 recurrent cases,6 /11 primary-onset cases;P =0.032）.The primary mutation in the recurrent cases occurred at codon 45 （S45F）,while codon 41 （T41A）was most frequently mutated in the primary -onset cases （P =0.002）.Conclusion Mutations in exon 3 of the β-catenin gene,particular-ly the S45F mutation,may represent risk factors for recurrence in pediatric patients and could potentially be used as prognostic factors.