Abstract
BackgroundNanoString’s Prosigna™ Breast Cancer Prognostic Gene Signature Assay is based on the PAM50 gene expression signature. The test outputs a risk of recurrence (ROR) score, risk category, and intrinsic subtype (Luminal A/B, HER2-enriched, Basal-like). The studies described here were designed to validate the analytical performance of the test on the nCounter Analysis System across multiple laboratories.MethodsAnalytical precision was measured by testing five breast tumor RNA samples across 3 sites. Reproducibility was measured by testing replicate tissue sections from 43 FFPE breast tumor blocks across 3 sites following independent pathology review at each site. The RNA input range was validated by comparing assay results at the extremes of the specified range to the nominal RNA input level. Interference was evaluated by including non-tumor tissue into the test.ResultsThe measured standard deviation (SD) was less than 1 ROR unit within the analytical precision study and the measured total SD was 2.9 ROR units within the reproducibility study. The ROR scores for RNA inputs at the extremes of the range were the same as those at the nominal input level. Assay results were stable in the presence of moderate amounts of surrounding non-tumor tissue (<70% by area).ConclusionsThe analytical performance of NanoString’s Prosigna assay has been validated using FFPE breast tumor specimens across multiple clinical testing laboratories.
Highlights
NanoString’s ProsignaTM Breast Cancer Prognostic Gene Signature Assay is based on the PAM50 gene expression signature
The PAM50 test was adapted to be performed using the nCounter Analysis System in order to develop a simplified workflow that could be performed in a local pathology lab (ProsignaTM Breast Cancer Gene Signature Assay, NanoString Technologies, site was NanoString Technologies (Seattle))
A recent clinical validation performed on RNA extracted from over 1000 formalin-fixed paraffin-embedded (FFPE) tumor specimens from the ATAC clinical trial demonstrated that the Prosigna risk of recurrence (ROR) score, based on the PAM50 gene expression signature, added significant prognostic information beyond the Oncotype DX® Recurrence Score® in estimating the likelihood of distant recurrence in hormone receptor positive, post-menopausal breast cancer patients [19] treated with endocrine therapy alone
Summary
NanoString’s ProsignaTM Breast Cancer Prognostic Gene Signature Assay is based on the PAM50 gene expression signature. The PAM50 test was adapted to be performed using the nCounter Analysis System in order to develop a simplified workflow that could be performed in a local pathology lab (ProsignaTM Breast Cancer Gene Signature Assay, NanoString Technologies, Seattle). This technology uses multiplexed gene-specific fluorescently-labeled probe pairs [17] to measure gene expression in frozen or formalin-fixed paraffin-embedded (FFPE) tissues with equivalent ease and efficiency [18]. Based in part on the results from these clinical studies and the analytical studies described NanoString obtained a CE Mark for its Prosigna assay in 2012, followed by US Food and Drug Administration (FDA) clearance in September of 2013
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