Analysis of protein expression patterns in Barrett's esophagus using MALDI mass spectrometry, in search of malignancy biomarkers.

SUMMARY: In order to detect early changes of malignant degeneration in Barrett's esophagus (BE), and to reduce the cost of surveillance, molecular biomarkers of early malignancy have been sought, with limited success, using genomic and immunohistochemical tools. We postulate that direct analysis of epithelial proteins using mass spectrometry will provide protein profiles capable of identifying patients at high risk of developing malignancy. Our aim is to find transitional protein signals that show a cancer profile within histologically benign BE, which can be used as indicators of early malignant change. Fourteen fresh-frozen, resected esophageal cancer specimens were analyzed using laser capture microdissection and matrix-assisted laser desorption/ionization mass spectrometry. Samples of squamous epithelium, and both benign and malignant Barrett's epithelium, were compared for differences in protein expression. Reliable differentiation of squamous and Barrett's epithelium was demonstrated. A comparison of benign and malignant Barrett's epithelium identified a number of cancer-specific protein peaks that were deletion or expression variations from benign epithelium. In four instances the proteins (7350, 8446, 10850, and 14693) appeared to be early malignant changes in histologically benign BE. Mass spectrometry performed upon fresh-frozen Barrett's epithelium, obtained by laser-capture microdissection, displays reproducible, tissue-specific, protein profiles. Distinct differences are demonstrated between benign and malignant epithelium, some of which appear to be candidate biomarkers of early malignant change. This technique reliably displays cellular protein expression in esophageal epithelium and deserves further study as a tool to identify early malignant degeneration in BE.