Abstract 816: A novel microRNA-based test demonstrates 92% accuracy in the classification of metastatic tumors from patients diagnosed with carcinoma of unknown primary .
Authors: Robert Wassman, Mats Sanden, George Pentheroudakis, Anna Goussia, Eti Meiri, Katerina Stoyianni, Danit Lebanony, George Fountzilas, Karin Ashkenazi, Vassiliki Malamou-Mitsi, Nicholas Palidis
Journal: Cancer Research (2013)

Abstract Background: Cancers of unknown primary origin (CUP) constitute 3%-5% (50,000 to 70,000 cases) of all newly diagnosed cancers per year in the United States. Including cancers of uncertain primary origin, the total number increases to 12%-15% (180,000 to 220,000 cases) of all newly diagnosed cancers per year in the United States. CUP is a major diagnostic and clinical challenge, since identifying the tissue-of-origin of metastases is crucial for selecting optimal treatment. MicroRNAs are a family of non-coding, regulatory short RNA molecules that are stable in clinical samples and are tissue-specific, consequently they have a great potential to be excellent biomarkers for cancer tissue-of-origin diagnosis. The goal of the study was to assess the performance of a microRNAs-based assay to diagnose the tissue of origin on a well annotated cohort of real CUP patients. Methods: A pre-developed microarray-based test that measures the expression of 64 microRNAs was employed to identify the tissue of origin of metastatic tumors of CUP cases. A cohort of 93 resected metastatic lesions with adequate tissue sample from 92 patients diagnosed with CUP was studied. 85 samples (84 patients) were processed successfully; eight samples failed due to inadequate RNA quality. Test results were compared with clinical presentation including imaging, pathological data (histology and IHC) and therapeutic response. Results: Overall, in 92% of the patients the assay results were fully concordant with the final clinical diagnosis based on all other clinical, pathologic and outcome data. There was a 22% improvement in agreement of the test results from the clinical Diagnosis at presentation to the final clinical Diagnosis (based on additional data gathered with patients’ treatment and follow up), which is a strong indication of the degree in which the assay facilitates the diagnostic process from early stages of patient's management. Conclusions: In a cohort of metastatic lesion samples from CUP patients, a previously developed test based on the expression profile of 64 microRNAs allowed accurate identification of tissue of origin in the vast majority of the cases. The high accuracy of this test in identifying the tissue of origin of metastasis of unknown primary has been validated by this study and demonstrates its clinical utility. The high concordance of the test results to the final diagnosis of the patient demonstrates the importance of the test to yield additional data valuable for patient's management at an early stage of patient's journey. This predictive ability could be associated with a change of clinical management, including administration of more effective chemotherapy combinations and targeted agents, in many of the patients in this study. Citation Format: Robert Wassman, Mats Sanden, George Pentheroudakis, Anna Goussia, Eti Meiri, Katerina Stoyianni, Danit Lebanony, George Fountzilas, Karin Ashkenazi, Vassiliki Malamou-Mitsi, Nicholas Palidis. A novel microRNA-based test demonstrates 92% accuracy in the classification of metastatic tumors from patients diagnosed with carcinoma of unknown primary . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 816. doi:10.1158/1538-7445.AM2013-816