Accurate classification of metastatic brain tumors using a novel microRNA-based test.

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e21044 Background: Identification of the tissue-of-origin (ToO) of a brain metastatic tumor is vital to its management. Carcinoma of unknown primary (CUP) is common in oncology, representing 4-6% of all invasive malignancies. A qRT-PCR-based test that measures the expression of 48 microRNAs was employed to identify the ToO of metastatic tumors of known origin as well as of CUP cases resected from brain or spine. Methods: A microRNA-based qRT-PCR diagnostic assay to identify the ToO of metastatic tumors was tested on 2 cohorts of resected brain and spinal metastatic lesions. The first cohort included 104 resected tumors with known origin (“reference diagnosis”), previously classified based on the patient's clinical history and pathological data. The second cohort included 57 tumors that had been originally diagnosed as CUP, for some of which additional clinical and pathological data was gathered following the original diagnosis. The majority of the samples were processed successfully (3 samples/cohort failed QA). Results: In this blinded study, the test predictions correctly identified the reference diagnosis of the samples with the known origin in 84% of the 89 cases (excluding prostate samples). In the second cohort, for 6 cases out of the 54 true CUP patients the diagnosis of the origin remained unknown clinically and after full pathological review. In 81% out of the remaining 48 CUP cases, the test prediction was in agreement with the diagnosis which was later confirmed clinically or with pathological data. In 19% out of the remaining CUP cases, the test results showed some discordance with the pathology or with clinical data. Additional clinical and pathological analysis of the CUP cases is currently ongoing. Conclusions: In a cohort of brain and spinal metastases, a previously developed qRT-PCR test based on the expression profile of 48 microRNAs allowed accurate identification of ToO in most of the cases. The high accuracy of this test in identifying the ToO of metastasis of unknown primary has been validated by this study and demonstrates its clinical utility. The test was also able to suggest origins in cases in which the pathological review was insufficient, suggesting additional clinical utility in those hard-to-resolve cases. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Rosetta Genomics Rosetta Genomics Rosetta Genomics