Accuracy of microRNA-based classification of metastases of unknown primary.

Abstract

10575 Background: Identification of the tissue of origin of metastatic tumors is important for estimation of prognosis and patient management. Carcinoma of unknown primary (CUP) is not uncommon in oncology, representing 3-5% of all newly found malignancies. We used a microarray-based test that uses the expression of 64 microRNAs to retrospectively evaluate tumors from CUP patients. Methods: A cohort of resected metastatic lesions from patients diagnosed with CUP was studied blindly on the microRNA-based test. The cohort included 93 samples (from 92 patients) with tissue adequate for the test. Eight samples failed due to inadequate RNA quality; 85 samples (84 patients) were processed successfully. Test results were compared with clinical presentation including imaging, pathological data (histology and IHC) at initial CUP diagnosis and with clinical management and outcome data at the completion of each patient`s follow up. Results: The test results were fully concordant with the diagnosis based on all the clinical and pathological information available including follow-up and outcome in 92% of patients compared to ~70% agreement with the patients’ diagnosis at initial presentation, before additional data gathered throughout patient management. Two different metastases from the same patient yielded the same result. The microRNA test assigned a single tissue of origin for 51 patients and two tissues of origin in 33 patients, with the first being the more likely diagnosis. When comparing only the first (or single) diagnosis, a concordant level of 88% was achieved. Conclusions: In a retrospective, well studied cohort of metastases from CUP patients, a previously developed test based on the expression profile of 64 microRNAs allowed accurate identification of tissue of origin in 92% of the cases. This study validates the high accuracy of the test on real CUP patients. The high concordance of the test results to the final tissue of origin diagnosis of the patient, even in cases where the initial diagnosis at CUP presentation was discordant, demonstrates the importance of the test in yielding additional data valuable for patient management at an early stage of the patient’s treatment plan.