True Positive vs. False Positive Staining

Immunohistochemical stains are indispensable for problem solving in diagnostic pathology. In order to evaluate them appropriately, it is critical to be aware of the characteristics of a true positive stain and a false positive stain. A "true positive" stain shows chromogen deposition in cells or structures that truly contain the antigen of interest. In contrast, a "false positive" stain is one where the chromogen is localized to cells or structures that in reality lack the antigen of interest. When using diaminobenzidine (DAB) chromogen with peroxidase-based detection systems, this problem can be expressed simply as "all that is brown is not real". Stains in which the entire section (both tumor and intervening non-neoplastic stroma) is a dark “muddy” brown are easily recognized by nearly any observer as falsely positive. Fewer observers realize that false positive staining commonly occurs in a different situation: where the tumor cells are strongly stained but the background non-neoplastic stroma is "clean" and free of chromogen deposition.