An antigen is a protein used to trigger an immune response in an animal. The animal responds by producing antibodies against an individual epitope or antigenic determining region located on the antigen. The antigen has several epitopes that can generate antibodies (Dalcik et al, 2012). The antigen can be enhanced by pretreatment with an antigen retrieval reagent that breaks protein cross-links formed by formalin fixation, thereby exposing an invisible antigenic site. There are different types of antigens like CD20, AE1, epithelial membrane antigen, MIB1, ER, CD43 and HMB45. Immunohistochemistry takes advantage of the reactive specificity that exists between an antibody and the corresponding antigen in tissues or cells. Antigen-antibody visualization complexes can be obtained by a number of colorimetric reactions, typically using a fluorescently labeled antibody or immunoperoxidase reporting system. When tissue is formalin fixed and paraffin embedded, this process sometimes results in a loss of antigenicity in the tissue. To overcome this problem, many different methods have been developed to reconstitute antigenicity by gently heating tissue sections once rehydrated in various mild saline solutions (D'Amico et al. 2009; Leong et al. 2010; Shi et al. .2011). Antigen retrieval methods cause the protein to unfold and then refold in the tissue, with the possibility that the unavailable epitope is now exposed and available for antibody binding. (Onul et al. 2012) There are many different methods that can be used for antigen retrieval, such as room temperature epitope retrieval method, such as hydrochloric acid methods and water method. formic acid. In heat-induced epitope retrieval, methods such as citrate buffer (pH6), citrate-EDTA bu...... middle of paper ...... nuclear immunostaining for epitope retrieval antigen. Shi SR's study shows that the nonspecific background was stronger and the reactivity of positive nuclei was low compared to those obtained by antigen retrieval techniques. The study also shows the difference in the solution used for antigen retrieval, the immunostaining intensity was satisfactory, especially in 5% urea solution and citric acid buffer, and in distilled water, a lower intensity was observed. The antigen retrieval technique is evolving; there may be different advances or approaches to improve immunostaining. Knowledge about presence in a specific approach differs for different antigens and different antibodies for different fixation durations and perhaps also for different fixatives. Original antigen retrieval techniques are now widely used and are important in organic chemistry research on formalin-fixed tissue sections..