Standardized Predictive Receptor Immunohistochemical Assays

Abstract

Tissue fixation is one of the processes that is central to the practice of surgical pathology. Despite the reliance on the process by the speciality, pathologists had little interest in the issue for most of the 20th century. Several factors were behind this general disinterest: Formalin was the universal fixative. Pathologists were generally under little or no pressure for speedy diagnoses. Prognostic factors (outcomes) were predicated on the diagnoses and staging of cancer specimens, whereas predictive (response to a specific therapy) assays were mostly biochemical. With the commercial release of the estrogen receptor (ER) antibody for immunohistochemical analysis in the early 1990s followed by the HER2 immunohistochemical assay several years later, predictive assays quickly transferred into the responsibility domain of surgical pathology. Most pathologists viewed predictive immunohistochemical assays to be similar to nonpredictive immunohistochemical assays, with little or no attention given to their accuracy (obtaining the correct or true result) or precision (same result each time) for the first several years of their use. Most assays were not standardized and, often, unique to the individual laboratory. Cut points for the percentage of stained cells needed for a positive result varied between laboratories and individual pathologists within the same department. The extent of the overall problem was well documented in an excellent series of quality management studies in which only 36% of the laboratories participating in external case monitoring had reliable receptor …