Pharmaceutical Sciences Faculty Publications

Proteomic Analysis of Formalin-Fixed Prostate Cancer Tissue

Document Type

Article

Publication Date

11-1-2005

Journal Title

Molecular & Cellular Proteomics

ISSN

1535-9476

Volume

4

Issue

11

First Page

1741

Last Page

1753

DOI

10.1074/mcp.M500102-MCP200

PubMed ID

16091476

Abstract

Proteomic analysis of formalin-fixed paraffin-embedded (FFPE) tissue would enable retrospective biomarker investigations of this vast archive of pathologically characterized clinical samples that exist worldwide. These FFPE tissues are, however, refractory to proteomic investigations utilizing many state of the art methodologies largely due to the high level of covalently cross-linked proteins arising from formalin fixation. A novel tissue microdissection technique has been developed and combined with a method to extract soluble peptides directly from FFPE tissue for mass spectral analysis of prostate cancer (PCa) and benign prostate hyperplasia (BPH). Hundreds of proteins from PCa and BPH tissue were identified, including several known PCa markers such as prostate-specific antigen, prostatic acid phosphatase, and macrophage inhibitory cytokine-1. Quantitative proteomic profiling utilizing stable isotope labeling confirmed similar expression levels of prostate-specific antigen and prostatic acid phosphatase in BPH and PCa cells, whereas the expression of macrophage inhibitory cytokine-1 was found to be greater in PCa as compared with BPH cells.

Keywords

Amino acid sequence, cytokines, formaldehyde, gene expression profiling, gene expression regulation, neoplastic, immunohistochemistry, mass spectrometry, microdissection, proteins, prostate, prostate-specific antigen, prostatic hyperplasia, proteome, proteomics, tissue fixation

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