Global mass spectrometry (MS) profiling and spectral count quantitation are used 
to identify unique or differentially expressed proteins and can help identify 
potential biomarkers. MS has rarely been conducted in retrospective studies, 
because historically, available samples for protein analyses were limited to 
formalin-fixed, paraffin-embedded (FFPE) archived tissue specimens. Reliable 
methods for obtaining proteomic profiles from FFPE samples are needed. Proteomic 
analysis of these samples has been confounded by formalin-induced protein 
cross-linking. The performance of extracted proteins in a liquid chromatography 
tandem MS format from FFPE samples and extracts from whole and laser capture 
microdissected (LCM) FFPE and frozen/optimal cutting temperature (OCT)-embedded 
matched control rat liver samples were compared. Extracts from FFPE and 
frozen/OCT-embedded livers from atorvastatin-treated rats were further compared 
to assess the performance of FFPE samples in identifying atorvastatin-regulated 
proteins. Comparable molecular mass representation was found in extracts from 
FFPE and OCT-frozen tissue sections, whereas protein yields were slightly less 
for the FFPE sample. The numbers of shared proteins identified indicated that 
robust proteomic representation from FFPE tissue and LCM did not negatively 
affect the number of identified proteins from either OCT-frozen or FFPE samples. 
Subcellular representation in FFPE samples was similar to OCT-frozen, with 
predominantly cytoplasmic proteins identified. Biologically relevant protein 
changes were detected in atorvastatin-treated FFPE liver samples, and selected 
atorvastatin-related proteins identified by MS were confirmed by Western blot 
analysis. These findings demonstrate that formalin fixation, paraffin 
processing, and LCM do not negatively impact protein quality and quantity as 
determined by MS and that FFPE samples are amenable to global proteomic 
analysis.