Accurate determination of cancer origin is necessary to guide optimal treatment but remains a diagnostic challenge. Gene expression profiling technologies have aided the classification of tumors and, therefore, could be applied in conjunction with clinicopathologic correlates to improve accuracy. We report an expanded version of the previously described 92-gene assay to classify 30 main tumor types and 54 histological subtypes, with coverage of ≥95% of all solid tumors based on incidence. Increased tissue coverage was achieved through expansion of a reference tumor database containing 2,206 specimens, with a median of 62 samples per main tumor type. The 92-gene classification algorithm demonstrated sensitivities of 87% and 85% for 30 main types and 54 histological subtypes, respectively, in leave-one-out cross validation, and 83% in a test set of 187 tumors representing 28 of the 30 main cancer types. These findings provide further support that broad and diverse tumor classification can be performed using a relatively compact gene set. An additional 300 consecutive cases submitted for clinical testing were profiled to characterize clinical utility in a real-world setting: the 92-gene assay confirmed 78% of samples having a single suspected primary tumor and provided a single molecular prediction in 74% of cases with two or more differential diagnoses. Further development of the 92-gene RT-PCR assay has resulted in a significant expansion in reportable tumor types and histological features with strong performance characteristics and supports the use of molecular classification as an objective standardized adjunct to current methods.
Copyright © 2011 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.