The principle of IHC has existed since the 1930s, but it was not until 1941 that the first IHC study was reported. Coons and his coworkers used Fluorescein isothiocyanate (FITC)-labeled antibodies to localize Pneumococcal antigens in infected tissues. Since then, with improvement and development of protein conjugation, enzyme labels have been introduced, such as peroxidase and alkaline phosphatase.
Colloidal gold label has also been discovered and used to identify immunohistochemical reactions at both light and electron microscopy levels. Other labels include radioactive elements, and the immunoreaction can be visualized by autoradiography. All of these make immunohistochemistry a routine and essential tool in diagnostic and research laboratories.