Tissue Profiling by MALDI Mass Spectrometry Distinguishes Clinical Grades of Soft Tissue Sarcomas

Abstract

Soft tissue sarcomas are rare, heterogeneous, mesenchymal tumors that have been poorly classified. The heterogeneity of these aggressive tumors has made consistent tumor grading difficult and accurately predicting the behavior of the tumor based on the histological subtype and grade has been challenging. Molecular profiling of proteins in tissues may present a new avenue for distinguishing clinical grades and overall tumor aggressiveness. Direct tissue analysis using matrix-assisted laser desorption ionization mass spectrometry is a new technology that permits rapid detection of hundreds of proteins from intact tissues. We have employed this technology to profile human soft tissue sarcomas to discover protein biomarkers that distinguish tumor grade. Profiling was accomplished on histologically-stained tissue sections, allowing highly reproducible spectra for each sarcoma grade to be obtained. Forty-two tissue specimens were analyzed in this manner. Several proteins specific for high-grade sarcomas were identified and confirmed with immunohistochemistry. Proteins present in control tissue, that are suppressed by soft tissue sarcomas, were also identified.