title: Molecular classification of cancer with the 92-gene assay in cytology and limited tissue samples.
abstract: BACKGROUND
  Detailed 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.
  
  
  METHODS
  Clinical 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Elena F
authors.initials: EF
authors.lastname: Brachtel
authors.affiliation: Biotheranostics, Inc., San Diego, California, USA.
authors.forename: Theresa N
authors.initials: TN
authors.lastname: Operaña
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
authors.forename: Peggy S
authors.initials: PS
authors.lastname: Sullivan
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Kerr
authors.affiliation: Biotheranostics, Inc., San Diego, California, USA.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Cherkis
authors.affiliation: Biotheranostics, Inc., San Diego, California, USA.
authors.forename: Brock E
authors.initials: BE
authors.lastname: Schroeder
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Dry
authors.affiliation: Biotheranostics, Inc., San Diego, California, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Schnabel
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D015331:Cohort Studies; D003581:Cytodiagnosis / Q000379:methods*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D009369:Neoplasms / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor
keywords: biological markers; clinical oncology; cytology; gene expression profiling; molecular targeted therapy