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Patient Outcomes Linked To Biomarker Levels
JonN writes to tell us Science Daily is reporting that researchers at Yale University have discovered that current pathology methods for biomarker detection can be dramatically altered depending on the concentration of antibodies used. From the article: "Biomarkers may have the power to provide diagnostic, therapeutic, and prognostic information for personalized medicine." said Donald Earl Henson, M.D., of the George Washington University Cancer Institute, in "Back to the Drawing Board on Immunohistochemistry and Predictive Factors," an accompanying editorial. "However, immunohistochemistry, a popular technique for evaluating biomarker expression, may contain procedural flaws that jeopardize its promise."
Currently, if someone has a disease, doctors use a variety of pathology techniques to characterize a disease. In the age of molecular medicine, doctors often do biopsies and determine the levels of various important proteins, or "biomarkers," made by the tumor. The level of these different proteins can be used for prognosis or treatment; for example, cancers with high levels of a protein called MMP9 tend to be metastatic and should be treated aggressively.
The problem comes when trying to measure the amount of protein. Most proteins are measured using immunohistochemistry, which just means that you "stain" the sample's proteins with antibodies specific for that protein. You then measure the amount of antibody through various methods; the antibodies are often attached to a fluorescent tag, and you measure the level of fluorescence and extrapolate the true protein concentration from that. You usually assume that the more antibody that binds, the more protein there is, and the two are related in a linear fashion. This is an important assumption.
Different pathologists use different concentrations of antibody. The article states that depending on what concentration you use, you can make completely opposite conclusions about the protein levels, and thus about the disease. Essentially, the flaw is that "there is a non-linear relationship between the antibody concentration and its target." In other words, adding a lot of antibody changes the way the antibody binds to the protein, which makes identifying the true protein amount much more difficult.
I hope that helps.