Abstract 2506: Histology-directed lipid MALDI MS profiling can distinguish prostate cancer from normal epithelium.

Abstract

Abstract Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is demonstrated to be useful for profiling of common solid tumors. In this approach, mass spectra are obtained from discrete locations on 10 μm-thick cryosection tissue, guided by H&E-stained top slide. To determine if a lipid signature obtained from tissue samples could be found to assist with diagnosis, frozen surgical samples collected from 7 prostate cancer patients and 9 adjacent normal tissue samples were analyzed using matrix (DHB/CHCA)-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). When leave-one-out cross validation was performed using support vector machine, permutation p value for the cross-validated misclassification rate was statistically significant (p=0.04), suggesting that lipid profiles are clearly different between prostate cancer and adjacent normal tissue samples. One of the most striking difference between prostate cancer and normal tissue is the phosphatidylcholine (PC) 32:1 (m/z 798.6) overexpression (p=0.007, tumor/normal=2.4). In order to identify molecular mechanisms of PC 32:1 overexpression in prostate cancers, we performed immunohistochemical analyses for metabolic enzymes responsible for phosphatidylcholine biosynthesis. Prostate cancers overexpress choline kinases and phosphate cytidylyltransferases, known oncogenes which generate phosphatidylcholines, compared with adjacent normal tissue samples. Thus, lipid MALDI MS analysis captures a global alteration in lipid profile of prostate cancer tissue, potentially distinguishing cancerous epithelium from normal epithelium. To our knowledge, this study is the first comprehensive lipid profiling study in prostate cancer. This histology-directed MALDI MS approach enables rapid and sensitive identification of discriminatory lipids in cancerous epithelium of prostate cancers, even those with infiltrative growth. We are in the process of a large sample set (Supported by Korean Ministry of Education, Science, and Technology Grant 2012K001506). Citation Format: Seungho Choi, Jun Won Park, Weon Seo Park, Hark Kyun Kim, Kang Hyun Lee. Histology-directed lipid MALDI MS profiling can distinguish prostate cancer from normal epithelium. [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 2506. doi:10.1158/1538-7445.AM2013-2506 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.