Cardiolipins Are Biomarkers of Mitochondria-Rich Thyroid Oncocytic Tumors

Oncocytic tumors are characterized by an excessive eosinophilic, granular cytoplasm due to aberrant accumulation of mitochondria. Mutations in mitochondrial DNA occur in oncocytic thyroid tumors, but there is no information about their lipid composition, which might reveal candidate theranostic molecules. Here, we used desorption electrospray ionization mass spectrometry (DESI-MS) to image and chemically characterize the lipid composition of oncocytic thyroid tumors, as compared with nononcocytic thyroid tumors and normal thyroid samples. We identified a novel molecular signature of oncocytic tumors characterized by an abnormally high abundance and chemical diversity of cardiolipins (CL), including many oxidized species. DESI-MS imaging and IHC experiments confirmed that the spatial distribution of CLs overlapped with regions of accumulation of mitochondria-rich oncocytic cells. Fluorescent imaging and mitochondrial isolation showed that both mitochondrial accumulation and alteration in CL composition of mitochondria occurred in oncocytic tumors cells, thus contributing the aberrant molecular signatures detected. A total of 219 molecular ions, including CLs, other glycerophospholipids, fatty acids, and metabolites, were found at increased or decreased abundance in oncocytic, nononcocytic, or normal thyroid tissues. Our findings suggest new candidate targets for clinical and therapeutic use against oncocytic tumors. Cancer Res; 76(22); 6588-97. ©2016 AACR.