An antigen is a protein used to initiate the immune response in an animal. The animal reacts by producing antibodies against individual epitopes or antigenic determining regions located on the antigen. The antigen has multiple epitopes that can generate antibodies (Dalcik et al, 2012). Antigen can be enhanced by pretreatment with antigen retrieval reagent which breaks protein cross-links formed by formalin fixation, thus exposing the invisible antigenic site. There are different types of antigens such as 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 within the tissue or cell. Antigen-antibody display complexes can be obtained through a series of colorimetric reactions, typically using a fluorescently labeled antibody or an immunoperoxidase signaling system. When tissue is fixed in formalin and embedded in paraffin, this process sometimes results in the 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 in the tissue to unfold and then fold 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, for example in room temperature epitope retrieval method such as hydrochloric acid methods and formic acid method. In heat-induced epitope retrieval, methods such as citrate buffer (pH6), citrate-EDTA bu...... middle of paper ...... uclear immunostaining for antigen retrieval. Shi SR's study shows that the nonspecific background was stronger and the positive nuclear reactivity was weak compared to those obtained with antigen retrieval techniques. The study also shows the difference in the solution used for antigen retrieval, the intensity of immunostaining was satisfactory, especially in 5% urea solution and citric acid buffer, and less intensity. The antigen retrieval technique is changing; there may be advances or different approaches to improve immunostaining. The presence information in the specific approach differs for different antigens and different antibodies due to the variable duration of fixation and perhaps also due to different fixatives. The original antigen retrieval techniques are now widely used and are important in organic chemistry research on formalin-fixed tissue sections.