In situ DESI - MSI lipidomic profiles of breast cancer molecular subtypes and precursor lesions.

Clinically meaningful molecular subtypes for classification of breast cancers have been established, however, initiation and progression of these subtypes remain poorly understood. The recent development of desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) facilitates the convergence of analytical chemistry and traditional pathology, allowing chemical profiling with minimal tissue pre-treatment in frozen samples. Here we characterized the chemical composition of molecular subtypes of breast cancer with DESI-MSI. Regions of interest (ROI) were identified, including invasive breast cancer (IBC), ductal carcinoma in situ (DCIS), and adjacent benign tissue (ABT), and metabolomic profiles at 200μm elaborated using Biomap software and the Lasso method. Top ions identified in IBC regions included polyunsaturated fatty acids, deprotonated glycerophospholipids and sphingolipids. Highly saturated lipids, as well as antioxidant molecules [(taurine (m/z 124.0068), uric acid (m/z 167.0210), ascorbic acid (m/z 175.0241), and glutathione (m/z 306.0765)], were able to distinguish IBC form ABT. Moreover, luminal B and triple-negative subtypes showed more complex lipid profiles compared to Luminal A and HER-2 subtypes. DCIS and IBC were distinguished based on cell signaling and apoptosis-related ions [fatty acids (341.2100 and 382.3736 m/z) and glycerophospholipids (PE(P-16:0/22:6, m/z 746.5099, and PS(38:3), m/z 812.5440)]. In summary, DESI-MSI identified distinct lipid composition between DCIS and IBC and across molecular subtypes of breast cancer with potential implications for breast cancer pathogenesis.