As formalin fixation protects the morphology of cells and subcellular structures (including nucleus shape, cellular and nuclear membranes, intercellular contacts),  it is rightfully very popular in preserving tissue samples for subsequent  immuno -staining.
 
However, cell proteins undergo not only cross-linking, but also quite some chemical modifications of amino acids upon formalin fixation, and the key is to recover the antigen (epitope) back before mmunostainingi onroutinely collected and stored tissues. 

 

There are some buffers (High, Low, EDTA, Tris, Citrate etc.  ) that allow the epitope recovery, and for about 80% of antibodies that work in blot, one can find an appropriate buffer between them. 

Unfortunately, there is one issue many people are not really aware of: using a wrong recovery buffer may still result in what looks like specific staining, and may be taken as such, but in reality is a non-specific one.
 
Therefore, the safest way to recover epitopes is to maximally reverse the fixation and chemical modifications of amino acids; and to allow the protein molecules to re-fold back maximally close to their native state. We have created, probably the most reliable epitope recovery unit, the 2100 Retriever, and thus saw the creation of a universal buffer for tissue processing as our primary task. We have accomplished it successfully with  R-Universal buffer: it properly recovers all epitopes recoverable in Tris, EDTA, High, Low, Citrate and similar buffers.  Besides standard IHC, it allows to perform multi-colour immunofluorescent staining of formalin fixed tissues and cells. Just process FFPE sections and stain them as cryostat ones!