Optimization of Tumor Dissection Procedures Leads to Measurable Improvement in the Quality of Molecular Testing

Document Type

Article

Publication Date

10-1-2024

Publication Title

The Journal of molecular diagnostics

Abstract

Molecular tests have an inherent limit of detection (LOD) and, therefore, require samples with sufficiently high percentages of neoplastic cells. Many laboratories use tissue dissection; however, optimal procedures for dissection and quality assurance measures have not been established. In this study, several modifications to tissue dissection procedures and workflow were introduced over 4 years. Each modification resulted in a significant improvement in one or more quality assurance measures. The review of materials following dissection resulted in a 90% reduction in KRAS mutations below the stated LOD (P = 0.004). Mutation allele frequencies correlated best with estimated tumor percentages for pathologists with more experience in this process. The direct marking of unstained slides, use of a stereomicroscope, validation of extraction from diagnostic slides, and use of a robust, targeted next-generation sequencing platform all resulted in reduction of quantity not sufficient specimens from 20% to 25% to nearly 0%, without a significant increase in test failures or mutations below the LOD. These data indicate that post-dissection review of unstained slides and monitoring quantity not sufficient rate, test failure rate, and mutation allele frequencies are important tumor dissection quality assurance measures that should be considered by laboratories performing tissue dissections. The amendments to tissue dissection procedures enacted during this study resulted in a measurable improvement in the quality and reliability of this process based on these metrics.

Medical Subject Headings

Humans; Neoplasms; High-Throughput Nucleotide Sequencing; Mutation; Gene Frequency; Proto-Oncogene Proteins p21(ras); Limit of Detection; Molecular Diagnostic Techniques; Quality Control

PubMed ID

39067571

ePublication

ePub ahead of print

Volume

26

Issue

10

First Page

876

Last Page

887

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