Immunohistochemistry of Biomarkers

Abstract

Immunohistochemistry (IHC) has an essential role in the diagnostic evaluation of cancers, most commonly to help identify and subclassify tumors, but its utility in assessing biomarkers that are predictive of benefit or lack of benefit from specific chemotherapies is becoming increasingly important. When IHC is used for predictive marker testing, the assessment of the extent of protein expression may be even more important than the presence or absence of expression, but many variables affect the quantitative measurement of protein expression in routinely processed tissues, and these can have profound influences on the test results. Immunohistochemistry (IHC) has been a critical tool for pathologists for more than 20 years and is still used most frequently to determine cell lineage and tumor type. Because of its far greater specificity, IHC has essentially replaced most traditional histochemical stains once used for this purpose. IHC is also used to identify specific cellular constituents (e.g., basal and myoepithelial cells), which may help to determine the presence of malignancy and/or invasion and to diagnose infectious diseases, but its role in predictive marker testing to select or exclude patients for specific therapies is growing rapidly in frequency and importance. Until recently, only a few predictive markers were routinely assessed in all patients, but an increasing number are becoming a regular part of clinical management. Such tissue-based biomarkers, many assessed solely by IHC, may predict responsiveness (or lack of response) to specific drugs or to entire classes of chemotherapeutic agents; however, along with the discovery of new biomarkers and their clinical significance, we are increasingly recognizing problems related to variability in laboratory assessment.