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Ten percent neutral buffered formalin fixes tissue by cross-linking proteins, potentially causing a conformational change or “masking” of the antigenic epitope and leading to reduced or absent antibody reactivity. Different antigen retrieval techniques are used to unmask the epitope; however, many times it is not possible to retrieve the epitope and get optimal immunohistochemical staining. In these situations the use of IHC Zinc fixative, which is a milder fixative than formalin, is recommended.Zinc-fixed paraffin embedded sections show very good immunostaining with many leukocytes markers and depict tissue morphology comparable to formalin-fixationUse of antigen retrieval techniques on the zinc-fixed paraffin sections may further enhance the antibody reactivity in some casesThere are a few antigens that are not preserved by zinc-fixation. In these situations use of fresh frozen tissue for immunohistochemical staining is the only alternative.