Abstract POSTER-TECH-1122: Mass spectrometric imaging of ovarian cancer mouse model tissue: searching for high-grade serous carcinoma biomarkers

Abstract

Abstract High-grade serous carcinoma (HGSC) is the most common and deadliest ovarian cancer responsible for 90% of all ovarian cancer deaths. Studying the origin and early progression of this deadly cancer is critical in identifying biomarkers for early detection of the disease. Unfortunately, in the case of HGSC, it is virtually impossible to obtain early-stage human HGSC tissue samples because there is no diagnostic method capable of detecting early forms of HGSC. The recent breakthrough of an animal model (Dicer-Pten double-knockout mice) provides an invaluable opportunity to finally investigate the early tumor microenvironment. The model exhibits remarkable similarities to human HGSC, allowing greater insight into the biochemistry associated with nascent neoplastic changes within ovarian and fallopian tube tissues. An important aspect of determining potential biomarkers is to correlate any detected chemical changes with observed histological changes. To visualize the spatial distribution of chemical changes, tissue-based mass spectrometric imaging (MSI) can be employed as an unbiased way of visualizing the changes of proteins, metabolites, or both in cancer tissues. MSI is particularly useful for identifying molecules uniquely elevated or lowered in early tumor tissues, in which cell-type specific changes are expected to occur due to intratumoral microenvironment heterogeneity. In this study, two complementary MSI techniques – matrix-assisted laser desorption ionization (MALDI) and desorption electrospray ionization (DESI) mass spectrometry – are applied to thin tissue sections of Dicer-Pten mutant mouse ovaries and fallopian tubes. Several sulfatide lipids d18:1/C16:0, d18:1/C24:1 and d18:1/C24:0 have been implicated as potential biomarkers in human ovarian cancer. These metabolites, among others, are being included in a thorough MSI experiment to visualize molecular changes in multiple cell types in the microenvironment during early tumor progression. In addition to providing information about the early molecular changes taking place, the knowledge gained from this study will also help understand which specific cell types in the fallopian tube are more prone to early tumorigenesis. (Grant support: Marsha Rivkin Ovarian Cancer Challenge Grant) Citation Format: Martin R. L. Paine, Rachel V. Bennett, Jaeyeon Kim, M. Cameron Sullards, Martin M. Matzuk, Facundo M. Fernández. Mass spectrometric imaging of ovarian cancer mouse model tissue: searching for high-grade serous carcinoma biomarkers [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-TECH-1122.