This invention relates, e.g., to a composition that, at
room temperature, when contacted with a sample comprising phosphoproteins, can fix and stabilize cellular phosphoproteins, preserve
cellular morphology, and allow the sample to be frozen to generate a
cryostat frozen section suitable for
molecular analysis. The composition comprises (1) a fixative that is effective to fix the phosphoproteins, and that has a sufficient
water content to be soluble for a stabilizer and / or a permeability enhancing agent); (2) a stabilizer, comprising (a) a
kinase inhibitor and (b) a
phosphatase inhibitor and, optionally, (c) a
protease (e.g., proteinase) inhibitor; and (3) a permeability enhancing agent (e.g. PEG). Methods are described for preserving phosphoproteins, using such a composition. Also described are endogenous surrogate markers for monitoring
protein degradation, including the loss of posttranslational modifications (such as
phosphorylation), e.g. the following removal of a
cell or tissue from a subject; and exogenous molecular sentinels (e.g. phosphoproteins attached to
magnetic nanoparticles) that allow one to evaluate the
processing history of a cellular or tissue
population sample.