Abstract 4900: Development of a method for metabolomics and histology of tissue biopsies

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Metabolomics, the global study of small molecules in a biological sample, is performed with the goal of extracting, identifying, and quantifying metabolites. As such, the technology is ideal for identifying biomarkers for diagnostics and drug therapy. One of the limitations with the current practice for metabolite extraction is that sample destruction precludes additional uses of the sample. This is particularly troublesome for high value samples with limited availability, such as clinical tumor biopsies. Clinical biopsies are taken in order to histologically diagnose and gauge cancer aggressiveness. Thus, physically disrupting these valuable samples is not ideal, even though quantitative metabolomic data could enhance histopathologic evaluation. In order to improve the amount of information obtained from patient biopsies, we have developed a method (termed PReservation by Extraction and Fixation, PREF) by which metabolite extraction simultaneously preserves the tissue for histological analysis. Briefly, upon sample collection, the biopsy is placed directly in methanol. Methanol incubation serves to recover metabolites, precipitate proteins, and fix the tissue. Following overnight incubation, the solvent is removed, evaporated to dryness, and reconstituted in a proprietary mixture of recovery standards. The needle biopsies are placed in biopsy bags and cassettes and transferred to Molecular Fixative until processed for histology. Solvent sample aliquots are taken for analysis on GC/MS and LC/MS platforms. Raw mass spectrometry data files are automatically extracted using a proprietary informatics system that includes peak identification and compound identification software. Compared to the current state of the art method for metabolite extraction, PREF recovers equivalent numbers and types of biochemicals from the tissue specimen. Furthermore, PREF preserves the tissue biopsy sample such that cellular architecture is retained, allowing for pathological analysis by chemical staining (hematoxylin & eosin) and antibody binding (immunohistochemistry). We have developed a non-destructive method for efficient metabolite extraction from tumor biopsies combined with preservation of the tissue for histological analysis. It is our hope that this novel method will augment the current histopathologic diagnosis and classification of tumors through quantitative measures of biochemicals in the same tissue. Given that certain biochemicals have been shown to correlate with disease aggressiveness, it is likely that this method will be valuable in helping to differentiate cancer aggressiveness. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4900. doi:10.1158/1538-7445.AM2011-4900