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

Autor: Fisch AS; Departments of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. afisch1@mgh.harvard.edu., Farahani AA; Immuto Scientific, Cambridge, MA, USA., Thierauf J; Foundation Medicine, Inc, Boston, MA, USA., Iafrate AJ; Departments of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Lennerz JK; BostonGene Corporation, Waltham, MA, USA., Faquin WC; Departments of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Department of Pathology, Massachusetts Eye and Ear, Boston, MA, USA.
Jazyk: angličtina
Zdroj: Head and neck pathology [Head Neck Pathol] 2024 Oct 26; Vol. 18 (1), pp. 114. Date of Electronic Publication: 2024 Oct 26.
DOI: 10.1007/s12105-024-01719-1
Abstrakt: 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 (R 2  = 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.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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