Abstract
Abstract Prostate cancer is often heterogeneous with multiple tumor foci within the same prostate. MALDI (Matrix-Assisted Laser Desorption/Ionization) mass spectrometry imaging (MSI) allows for a comprehensive profiling of the molecular phenotype on the protein, peptide, lipid, and metabolite level across entire tissue slides without prior enrichment of tumor cells. This study aims in a MALDI-based discrimination of cancer areas that are heterogeneous with respect to morphology and molecular features. We established a method for cryopreservation of entire prostates from cancer patients, and build tissue microarrays from individual cancerous prostates representing >30 different areas of the primary tumor as well as multiple lymph node metastases. We analyzed these arrays for ERG fusion by FISH and for peptide signatures by MALDI MSI. In addition, 2 selected tumor areas and 4 different lymph node metastases from one prostate were subjected to paired end next generation sequencing. MALDI identified 5 masses that were specific for epithelial cells. One particular mass was strongly related to presence of ERG fusion. In one prostate, we identified another mass that was present only in 2/35 tissue spots from the primary tumor as well as in 4/10 lymph nodes. Deep sequencing of different tumor areas of this case identified distinct patterns of structural genetic alterations. A cluster analysis showed that all samples were clonally related, and identified the area inside the primary tumor that gave rise to the metastases. In conclusion, these data suggest that MALDI imaging and next generation sequencing allow for identification of genetic and proteome patterns that correspond to metastatic spread of prostate cancer cells. A combination of both techniques is suited to dissect the genetic background of distinct MALDI signatures. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1272. doi:1538-7445.AM2012-1272
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