title: Blinded comparator study of immunohistochemical analysis versus a 92-gene cancer classifier in the diagnosis of the primary site in metastatic tumors.
abstract: 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.
authors.affiliation: Clarient Inc., Aliso Viejo, California, 92656, USA. lweiss@clarientinc.com
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Weiss
authors.forename: Peiguo
authors.initials: P
authors.lastname: Chu
authors.forename: Brock E
authors.initials: BE
authors.lastname: Schroeder
authors.forename: Veena
authors.initials: V
authors.lastname: Singh
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mark G
authors.initials: MG
authors.lastname: Erlander
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Schnabel
mesh_terms: D006801:Humans; D007150:Immunohistochemistry; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D059467:Transcriptome