Potential clinical utility of gene-expression profiling in identifying tumors of uncertain origin

To evaluate the potential impact of a gene-expression-based test on the diagnosis of primary tumors in difficult-to-diagnose cases.

The Tissue of Origin Test uses 2000 gene measurements to classify the most likely primary tumor. We categorized 284 consecutive samples by pretest diagnosis, then recategorized the samples using test results to identify cases with changes in diagnosis.

A total of 64% of incoming diagnoses were nonspecific. A leading diagnosis for the primary site was provided for remaining cases, indicating an unresolved differential. Overall, the test predicted a change in the most likely primary site, either a change from nonspecific to specific site or a change from one specific primary site to another in 81% of the cases and confirmed the suspected primary site for 15% of cases.

A new molecular diagnostic has the potential to change both primary site identification and therapy selection for the majority of patients tested.