Formalin-fixed, paraffin-embedded mechanisms

In 1991 Shi et al. published their seminal observation that high-temperature incubation of formalin-fixed, paraffin-embedded (FFPE) tissue sections in buffers for short periods led to improved immunohistochemical staining.1 However, more than 15 years later, heat-induced antigen retrieval (AR) remains largely an empirical procedure, requiring the optimization of several critical parameters by trial and error.2,3 Further improvements in AR will require an in-depth understanding of the chemistry of formaldehyde fixation and the molecular mechanism(s) underlying the AR method. 

This juxtaposes the bcl-1 locus to the immunoglobulin (Ig) gene sequences and leads to deregulation of cyclin Dl. A similar translocation is present in a subset of multiple myeloma but is not present in hairy cell leukemia. The mechanism of overexpression of cyclin-D 1 in hairy cell leukemia is unknown. Detection of the expression of Bcl-1 is less helpful in establishing a diagnosis of mantle cell lymphoma. Several clones are available for the detection of this antigen in formalin fixed paraffin embedded material however, rabbit monoclonal antibodies are the most robust. The level of cyclin-D 1 in mantle cell lymphomas, multiple myeloma, and hairy cell leukemia is much less than in epithelial tumors and even normal tissue and one must use cases of mantle cell lymphoma to successfully establish validation of your selected immunohistochemical platform. 

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