Precision Needle-Punch Tumor Enrichment From Paraffin Blocks Improves the Detection of Clinically Actionable Genomic Alterations and Biomarkers

Authors

Douglas I Lin
Richard S P Huang
Ioannis Ladas
Rachel B Keller
Nimesh R Patel
Sotirios Lakis
Brennan Decker
Tyler Janovitz
Douglas A Mata
Jeffrey S Ross
Jo-Anne Vergilio
Julia A Elvin
Roy S Herbst
Philip C Mack
Jonathan K Killian

Publication Date

1-1-2024

Journal

Frontiers in Oncology

Abstract

BACKGROUND: While many molecular assays can detect mutations at low tumor purity and variant allele frequencies, complex biomarkers such as tumor mutational burden (TMB), microsatellite instability (MSI), and genomic loss of heterozygosity (gLOH) require higher tumor purity for accurate measurement. Scalable, quality-controlled, tissue-conserving methods to increase tumor nuclei percentage (TN%) from tumor specimens are needed for complex biomarkers and hence necessary to maximize patient matching to approved therapies or clinical trial enrollment. We evaluated the clinical utility and performance of precision needle-punch enrichment (NPE) compared with traditional razor blade macroenrichment of tumor specimens on molecular testing success.

METHODS: Pathologist-directed NPE was performed manually on formalin-fixed, paraffin embedded (FFPE) blocks. Quality control of target capture region and quantity of residual tumor in each tissue block was determined via a post-enrichment histologic slide recut. Resultant tumor purity and biomarker status were determined by the computational analysis pipeline component of the FDA-approved next-generation sequencing (NGS) assay, FoundationOne

RESULTS: In real-world clinical samples, enrichment rate via NPE was increased to ~50% over a 2.5-year period, exceeding the prior use of razor blade macro-enrichment (

CONCLUSIONS: Pathologist-directed precision enrichment from tissue blocks (aka NPE) increases tumor purity, and consequently, yields a greater number of successful tests and complex biomarker determinations. Moreover, this process is rapid, safe, inexpensive, scalable, and conserves patient surgical pathology material. NPE may constitute best practice with respect to enriching tumor cells from low-purity specimens for biomarker detection in molecular laboratories.

Keywords

tumor enrichment, tumor purity, biomarker, molecular diagnosis, FoundationOne®CDx, tumor microdissection, next generation sequencing, biomarkers

Comments

PMID: 38444675