IHC4 Assay
The IHC4 assay is based on a multivariate model that uses semiquantitative information from immunohistochemical assessment of ER, PR, HER2 and Ki67. The assay is performed on formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimens and a risk score for recurrence is calculated by an algorithm.
While the IHC4 test is elegant in its simplicity and has similar performance characteristics to the more complex and expensive commercial tests, it uses information from ER, PR and Ki67 differently to how these markers are currently interpreted in routine practice. Physicians tend to use these markers as binary categories (that is, ER-positive vs. ER-negative, Ki67 low vs. Ki67 high, and so forth) and create distinct groups (with four binary markers, 16 different marker groups are possible); in contrast, IHC4 uses a mathematical formula that weighs the semiquantitative expression values and combines these into a single risk score. The mathematical equation behind the IHC4 score is public; however, in the absence of standardized quantification of each of the four variables that would match the IHC assay sensitivity and the dynamic ranges used in the seminal paper, applying the formula to local pathology results could be highly misleading.