Detection of the epidermal growth factor receptor, amphiregulin and epiregulin in formalin-fixed paraffin-embedded human placenta tissue by matrix-assisted laser desorption/ionization mass spectrometry imaging

The study of the expression and the tissue distribution of the tyrosine kinase drug-target EGFR is of interest in oncology as a marker of potential efficacy of treatment. It has been reported, however, that the response rates to anti-EGFR drugs are poorly linked to its expression. Clinical studies have also revealed a patient response correlation with the expression levels of two EGFR ligands; amphiregulin and epiregulin. Here we report the development of a matrix assisted laser desorption ionisation mass spectrometry imaging methodology for the study of EGFR, epiregulin and amphiregulin distribution in formalin fixed paraffin embedded Human placental tissue and a comparison to expression patterns obtained by immunohiostochemistry. Using on-tissue digests and imaging of specific peptides, the tissue distribution of these proteins has been obtained down to 30µm spatial resolution.

Keywords: MALDI, tissue imaging, recombinant cancer therapeutics, EGFR, amphiregulin, epiregulin, FFPE, placenta, Cetuximab, Panitumumab, immunohistochemistry, colorectal cancer, targeted drugs