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Blinded Comparator Study of Immunohistochemical Analysis versus a 92-Gene Cancer Classifier in the Diagnosis of the Primary Site in Metastatic Tumors

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Accurate tumor classification is fundamental to inform predictive biomarker testing and optimize therapy. Gene expression–based tests are proposed as diagnostic aids in cases with uncertain diagnoses. This study directly compared the diagnostic accuracy of IHC analysis versus molecular classification using a 92-gene RT-PCR assay for determination of the primary tumor site. This prospectively defined blinded study of diagnostically challenging cases included 131 high-grade, primarily metastatic tumors. Cases were reviewed and reference diagnoses established through clinical correlation. Blinded FFPE sections were evaluated by either IHC/morphology analysis or the 92-gene assay. The final analysis included 122 cases. The 92-gene assay demonstrated overall accuracy of 79% (95% CI, 71% to 85%) for tumor classification versus 69% (95% CI, 60% to 76%) for IHC/morphology analysis (P = 0.019). Mean IHC use was 7.9 stains per case (median, 8; range, 2 to 15). IHC/morphology analysis accuracy was 79%, 80%, and 46% when 1 to 6 (n = 42), 7 to 9 (n = 41), and >9 (n = 39) IHC stains were used, respectively, versus 81%, 85%, and 69%, respectively, with the 92-gene assay. Results from this blinded series of high-grade metastatic cases demonstrate superior accuracy with the 92-gene assay versus standard-of-care IHC analysis and strongly support the diagnostic utility of molecular classification in difficult-to-diagnose metastatic cancer.

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Supported by research funding from bioTheranostics Inc. (L.M.W. and P.C.).

Disclosures: B.E.S., V.S., Y.Z., M.G.E., and C.A.S. are employees and stockholders of bioTheranostics Inc., and L.M.W. is a member of the Medical Advisory Board of bioTheranostics Inc. The 92-gene assay (CancerTYPE ID) described is a laboratory-developed test commercialized by bioTheranostics Inc.