JOURNAL ARTICLE
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Diagnosis of metastatic neoplasms: molecular approaches for identification of tissue of origin.

CONTEXT: Tumors of uncertain or unknown origin are estimated to constitute 3% to 5% of all metastatic cancer cases. Patients with these types of tumors show worse outcomes when compared to patients in which a primary tumor is identified. New molecular tests that identify molecular signatures of a tissue of origin have become available.

OBJECTIVE: To review the literature on existing molecular approaches to the diagnosis of metastatic tumors of uncertain origin and discuss the current status and future developments in this area.

DATA SOURCES: Published peer-reviewed literature, available information from medical organizations (National Comprehensive Cancer Network), and other publicly available information from tissue-of-origin test providers and/or manufacturers.

CONCLUSIONS: Molecular tests for tissue-of-origin determination in metastatic tumors are available and have the potential to significantly impact patient management. However, available validation data indicate that not all tests have shown adequate performance characteristics for clinical use. Pathologists and oncologists should carefully evaluate claims for accuracy and clinical utility for tissue-of-origin tests before using test results in patient management. The personalized medicine revolution includes the use of molecular tools for identification/confirmation of the site of origin for metastatic tumors, and in the future, this strategy might also be used to determine specific therapeutic approaches.

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