Comparative Analysis of MYB Expression by Immunohistochemistry and RNA Sequencing in Clinical Gene Fusion Detection in Adenoid Cystic Carcinoma.

IF 3.2 Q2 PATHOLOGY Head & Neck Pathology Pub Date : 2024-10-26 DOI:10.1007/s12105-024-01719-1
Adam S Fisch, Alexander A Farahani, Julia Thierauf, A John Iafrate, Jochen K Lennerz, William C Faquin
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Abstract

Purpose: MYB has been shown to play a central role in oncogenesis in a majority of adenoid cystic carcinomas (ACC). Testing for MYB expression via immunohistochemistry (IHC) or testing for the MYB gene fusion by next-generation sequencing (NGS) have become useful tools for the diagnosis of ACC. In addition, detection of MYB expression may have implications for patient management.

Methods: A cohort of 35 ACC cases was identified from the archival pathology files of the Massachusetts General Hospital. Cases were tested for MYB expression using a panel of 4 different commercially available MYB antibodies and scored using a modified Allred system. RNA-based NGS for MYB gene fusion detection was also performed.

Results: Among 4 different MYB antibodies, the sensitivity for MYB detection ranged from 26 to 97%. When a 30% threshold for determination of MYB immunohistochemical positivity was used, the AB_10900735 IHC clone showed the maximum sensitivity (97%). RNA sequencing revealed 19 (54%) cases positive for MYB fusions, and expression analysis derived from the sequencing data confirmed a significant association between MYB expression and fusion status (p = 0.036). Although less sensitive, the AB_778878 MYB clone showed a significant positive association between IHC staining and MYB RNA expression (R2 = 0.15, p = 0.023).

Conclusion: The detection of MYB expression using immunohistochemistry varies significantly depending on the antibody used. Comparison with MYB fusion and transcription levels, as determined by NGS, reveals that MYB has a complex relationship between genetic alterations, transcript levels, and protein abundance.

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腺样囊性癌临床基因融合检测中免疫组织化学与 RNA 测序对 MYB 表达的比较分析
目的:MYB已被证明在大多数腺样囊性癌(ACC)的致癌过程中起着核心作用。通过免疫组织化学(IHC)检测 MYB 表达或通过下一代测序(NGS)检测 MYB 基因融合已成为诊断 ACC 的有用工具。此外,MYB表达的检测可能会对患者管理产生影响:方法:从马萨诸塞州总医院的病理档案中确定了 35 例 ACC 病例。使用 4 种不同的市售 MYB 抗体检测病例的 MYB 表达,并使用改良的 Allred 系统进行评分。此外,还进行了基于 RNA 的 NGS MYB 基因融合检测:结果:在 4 种不同的 MYB 抗体中,MYB 检测灵敏度在 26% 到 97% 之间。当使用 30% 的阈值来确定 MYB 免疫组化阳性时,AB_10900735 IHC 克隆显示出最高的灵敏度(97%)。RNA 测序显示 19 例(54%)MYB 融合阳性,根据测序数据进行的表达分析证实了 MYB 表达与融合状态之间存在显著关联(p = 0.036)。AB_778878 MYB 克隆虽然敏感性较低,但在 IHC 染色和 MYB RNA 表达之间显示出明显的正相关(R2 = 0.15,p = 0.023):结论:使用免疫组化方法检测 MYB 表达因所用抗体的不同而有很大差异。通过与 NGS 测定的 MYB 融合和转录水平进行比较,发现 MYB 在遗传改变、转录水平和蛋白质丰度之间存在复杂的关系。
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来源期刊
CiteScore
5.70
自引率
9.50%
发文量
99
期刊介绍: Head & Neck Pathology presents scholarly papers, reviews and symposia that cover the spectrum of human surgical pathology within the anatomic zones of the oral cavity, sinonasal tract, larynx, hypopharynx, salivary gland, ear and temporal bone, and neck. The journal publishes rapid developments in new diagnostic criteria, intraoperative consultation, immunohistochemical studies, molecular techniques, genetic analyses, diagnostic aids, experimental pathology, cytology, radiographic imaging, and application of uniform terminology to allow practitioners to continue to maintain and expand their knowledge in the subspecialty of head and neck pathology. Coverage of practical application to daily clinical practice is supported with proceedings and symposia from international societies and academies devoted to this field. Single-blind peer review The journal follows a single-blind review procedure, where the reviewers are aware of the names and affiliations of the authors, but the reviewer reports provided to authors are anonymous. Single-blind peer review is the traditional model of peer review that many reviewers are comfortable with, and it facilitates a dispassionate critique of a manuscript.
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