Molecular classification of cancer with the 92-gene assay in cytology and limited tissue samples.

Elena F Brachtel,Catherine A Schnabel,Theresa N Operaña,Sarah E Kerr,Karen A Cherkis,Sarah M Dry,Brock E Schroeder,Peggy S Sullivan

doi:10.18632/oncotarget.8449

Elena F Brachtel, Catherine A Schnabel + Show 6 more

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https://doi.org/10.18632/oncotarget.8449

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Abstract

BackgroundDetailed molecular evaluation of cytology and limited tissue samples is increasingly becoming the standard for cancer care. Reproducible and accurate diagnostic approaches with reduced demands on cellularity are an ongoing unmet need. This study evaluated the performance of a 92-gene assay for molecular diagnosis of tumor type/subtype in cytology and limited tissue samples.MethodsClinical validation of accuracy for the 92-gene assay in limited tissue samples such as cytology cell blocks, core biopsies and small excisions was conducted in a blinded multi-institutional study (N = 109, 48% metastatic, 53% grade II and III). Analytical success rate and diagnostic utility were evaluated in a consecutive series of 644 cytology cases submitted for clinical testing.ResultsThe 92-gene assay demonstrated 91% sensitivity (95% CI [0.84, 0.95]) for tumor classification, with high accuracy maintained irrespective of specimen type (100%, 92%, and 86% in FNA/cytology cell blocks, core biopsies, and small excisions, respectively; p = 0.26). The assay performed equally well for metastatic versus primary tumors (90% vs 93%, p = 0.73), and across histologic grades (100%, 90%, 89%, in grades I, II, and III, respectively; p = 0.75). In the clinical case series, a molecular diagnosis was reported in 87% of the 644 samples, identifying 23 different tumor types and allowing for additional mutational analysis in selected cases.ConclusionsThese findings demonstrate high accuracy and analytical success rate of the 92-gene assay, supporting its utility in the molecular diagnosis of cancer for specimens with limited tissue.

Highlights

While molecular testing in oncology continues to develop and validate new methodologies employing reduced cellularity, such as circulating tumor cells (CTCs) and cell-free tumor material, the current standard of care depends on appropriate management of tumor tissue biopsy specimens for diagnosis and ancillary studies [1, 2]
As the tissue samples obtained by minimally invasive diagnostic procedures continue to decrease in size, the demand increases for detailed diagnostic evaluation and molecular testing using these limited tissue samples [3]
The biopsy types evaluated for this data set included fine needle aspirations (FNAs)/ cell blocks (N = 20, 18%), core / other biopsies (N = 52, 48%), and small excisions (N = 37, 34%) (Table 1 and Figure 1)

Summary

Introduction

While molecular testing in oncology continues to develop and validate new methodologies employing reduced cellularity, such as circulating tumor cells (CTCs) and cell-free tumor material, the current standard of care depends on appropriate management of tumor tissue biopsy specimens for diagnosis and ancillary studies [1, 2]. Several diagnostic assays for gene expression-based classification of tumors requiring minimal tissue are already in use [7, 8] These molecular tools provide independent quantitative data that is standardized and complementary to routine morphology and immunohistochemistry (IHC) approaches [8,9,10]. Integrating gene expression profiling into diagnostic algorithms for samples that have limited cellular content or lack definitive morphological and immunohistochemical features allows the remaining tissue to be used for reflex biomarker testing [11]. The goal of these various approaches is to ensure accurate diagnosis and allocation of tissue from small samples for the appropriate ancillary studies. This study evaluated the performance of a 92-gene assay for molecular diagnosis of tumor type/subtype in cytology and limited tissue samples

Methods

Results

Conclusion