Evidence map›Paper›PMID 38896376›Full record

ArticleHead and neck pathology2024

A Novel Scoring System for MYB RNA In Situ Hybridization Displays High Sensitivity and Specificity for Adenoid Cystic Carcinoma in a Clinical Setting.

Mariel Bedell, Dale W Lewis, Raja R Seethala

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Article in Head and neck pathology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

3 authors.

Mariel BedellDepartment of Pathology and Laboratory Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. bedellml@upmc.edu.ORCID http://orcid.org/0009-0003-2877-119X
Dale W LewisDepartment of Pathology and Laboratory Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Raja R SeethalaDepartment of Pathology and Laboratory Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-3617-075X

Funding

University of Pittsburgh Clinical and Translational Science InstituteUL1TR001857 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2016 to 2025
$129.3M
Clinical and Translational Sciences Institute at the University of Pittsburgh Grant Number UL1-TR-001857NCATS NIH HHS UL1 TR001857
6 · The paper itself

Abstract

backgroundMYB RNA in situ hybridization (ISH) has emerged as a reliable and accessible marker to support adenoid cystic carcinoma (ACC) diagnosis, though still not well studied. Here, we report our results in a validation and prospective cohort to improve MYB RNA ISH diagnostic accuracy.

methods79 cases (23 retrospective and 56 prospective) underwent MYB RNA ISH testing (44 ACC and 35 non-ACC). MYB RNA ISH results were initially interpreted based on previously established (original) scoring criteria. Weighted "i-scores", percent positive tumor cells, percent tumor cells with large signals (% LS), and staining pattern (abluminal, diffuse, focal non-patterned, or negative) were inputs for logistic regression models. Final model performance characteristics were compared with original scoring criteria and MYB::NFIB FISH results.

resultsAn abluminal pattern was characteristic and exclusive to ACC. All i-scores, % LS, and percent positive were significantly higher in ACC. Original scoring criteria yielded a 95.5% sensitivity (Sn), 68.6% specificity (Sp), and 83.5% accuracy. MYB::NFIB FISH yielded a 42.9% sensitivity, 100% specificity, and 60% accuracy. Optimizing for performance, simplicity, and minimal collinearity, our final model was defined as: abluminal pattern and/or % LS > 16.5%, which resulted in a 93.2% Sn, 97.1% Sp, and 94.9% accuracy for ACC diagnosis. False negatives included an ACC with striking tubular eosinophilia and a MYBL1::NFIB translocated ACC. One false positive exclusive to the final model was a nasopharyngeal carcinoma with MYB amplification.

conclusionsMYB RNA ISH has a higher Sn than MYB::NFIB FISH while retaining high Sp. Our model provides improvements to specificity compared to original scoring criteria and highlight the importance of abluminal staining pattern and % LS. Nonetheless, alternate fusions remain key false negatives while rare non-ACC with other mechanisms of MYB activation may present as false positives.

Indexed as

Biomarkers, TumorCarcinoma, Adenoid CysticProto-Oncogene Proteins c-mybSensitivity and SpecificityAdultAgedAged, 80 and overFemaleHumansIn Situ HybridizationIn Situ Hybridization, FluorescenceMaleMiddle AgedProspective StudiesRetrospective StudiesYoung AdultBiomarkers, TumorMYB protein, humanProto-Oncogene Proteins c-mybAdenoid cystic carcinomaHybridizationIn situLogistic regressionmRNAMyb geneQuantitative scoringSalivary gland neoplasms

Identifiers

PMID38896376
PMCPMC11187024

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.