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Tissue Histology: Preserving Information from Molecules
Jaleh Mansouri, M.D.
Tissue processing comprises a basic step in diagnostic pathology but often
involves organic chemicals such as formaldehyde that may destroy the integrity of
molecules. Fixatives like formalin cross-link nucleic acids and proteins. This process
alters the physicochemical structures of these molecules thus rendering them less
amenable to intact retrieval from paraffin-embedded tissue. Macromolecules such as
phosphoproteins and RNA (ribonucleic acid) serve as critical sources of diagnostic and
prognostic information, especially in tumor pathology assays (eg Mammoprint, Oncotype
Dx). While snap freezing is often performed to preserve tissues for molecular analysis,
resulting histomorphology is not optimal and may contain freeze artifacts. For these
reasons, researchers have focused on developing novel fixatives that protect molecules in
paraffin-embedded tissue for future molecular testing.
One example of an innovative technology is the PAXgene tissue system
(PreAnalytiX). This system use formalin-free solution and rapid fixation that aim to
preserve both histology and macromolecules such as DNA and RNA. While this
technology is promising as a tissue processing tool for both histologic diagnosis and
molecular analysis, more studies are needed to evaluate the accuracy and validity of this
technology compared to standard formalin fixation in regard to tissue diagnosis and
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