BRAF Exon 15 Mutations in the Evaluation of Well-Differentiated Epithelial Nephroblastic Neoplasms in Children: A Report From the Children's Oncology Group Study AREN03B2.

IF 3.7 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY
Jeffery A Goldstein, Lindsay A Renfro, Lawrence J Jennings, Elizabeth A Mullen, James Geller, Kelly Vallance, Conrad V Fernandez, Elizabeth J Perlman
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Abstract

Context.—: The distinction between well-differentiated epithelial favorable-histology Wilms tumor (EFHWT) and metanephric adenoma (MA) in children has historically been determined by the required absence of both a fibrous pseudocapsule and mitotic activity in MA. More recently these features have been allowed in adult MA. Mutations in exon 15 of the BRAF gene are reported in up to 88% of MAs but have not been reported in EFHWTs in children lacking MA features.

Objective.—: To clarify the pathologic and molecular features used to distinguish between pediatric MA and EFHWT.

Design.—: Stage I epithelial tumors classified as EFHWT on central review (36 patients) were identified from the Children's Oncology Group AREN03B2 study. Thirteen tumors had morphologic features overlapping those of MA and 23 lacked such features; 35 of 36 had tissue available for sequencing of BRAF.

Results.—: Patients with EFHWTs with MA features (13) were older (mean, 8.4 versus 1.9 years; P < .001), had smaller tumor diameters (mean, 6.0 versus 9.7 cm; P < .001), and had fewer mitoses (mean, 1 versus 48 mitoses per 10 high-power fields; P < .001) than patients with EFHWT lacking MA features (23). All EFHWTs with MA features contained at least a partial fibrous pseudocapsule; 7 of 12 (58%) had a BRAF exon 15 mutation. No BRAF exon 15 mutations were identified in 23 EFHWTs lacking MA features. None of the 13 EFHWT patients with MA features have experienced relapse (median follow-up 5.9 years).

Conclusions.—: Pediatric epithelial neoplasms with features of MA that show partial encapsulation and/or modest mitotic activity may be classified as MAs. Although BRAF mutation supports the diagnosis of MA, it is not required for the diagnosis.

儿童分化良好的上皮性肾母细胞肿瘤评估中的 BRAF 15 号外显子突变:儿童肿瘤学组 AREN03B2 研究报告》。
背景:儿童分化良好的上皮好组学 Wilms 肿瘤(EFHWT)与肾上腺瘤(MA)的区别,历来是根据肾上腺瘤必须没有纤维假包囊和有丝分裂活动来确定的。最近,成人肾腺瘤也出现了这些特征。据报道,BRAF 基因第 15 外显子的突变在高达 88% 的 MA 中存在,但在 EFHWT 中尚未见报道:明确用于区分儿科 MA 和 EFHWT 的病理和分子特征:从儿童肿瘤学组 AREN03B2 研究中确定了经中央审查归类为 EFHWT 的 I 期上皮肿瘤(36 例患者)。其中 13 例肿瘤的形态学特征与 MA 重叠,23 例肿瘤缺乏此类特征;36 例肿瘤中有 35 例肿瘤组织可用于 BRAF 测序:与缺乏 MA 特征的 EFHWT 患者(23 例)相比,具有 MA 特征的 EFHWT 患者(13 例)年龄较大(平均 8.4 岁对 1.9 岁;P < .001),肿瘤直径较小(平均 6.0 厘米对 9.7 厘米;P < .001),有丝分裂较少(平均每 10 个高倍视野中有 1 个有丝分裂对 48 个有丝分裂;P < .001)。所有具有 MA 特征的 EFHWT 至少含有部分纤维性假包囊;12 例中有 7 例(58%)发生了 BRAF 15 号外显子突变。在 23 例无 MA 特征的 EFHWT 中未发现 BRAF 15 号外显子突变。在13名具有MA特征的EFHWT患者中,没有一人复发(中位随访5.9年):结论:具有MA特征的小儿上皮性肿瘤表现为部分包膜和/或适度的有丝分裂活动,可归类为MA。虽然 BRAF 基因突变有助于 MA 的诊断,但并非诊断的必要条件。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
9.20
自引率
2.20%
发文量
369
审稿时长
3-8 weeks
期刊介绍: Welcome to the website of the Archives of Pathology & Laboratory Medicine (APLM). This monthly, peer-reviewed journal of the College of American Pathologists offers global reach and highest measured readership among pathology journals. Published since 1926, ARCHIVES was voted in 2009 the only pathology journal among the top 100 most influential journals of the past 100 years by the BioMedical and Life Sciences Division of the Special Libraries Association. Online access to the full-text and PDF files of APLM articles is free.
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