Researchers in the Department of Pathology at Yale University School of Medicine report that when using current pathology methods of biomarker detection, the concentration of antibodies used dramatically alters the apparent relationship of biomarker level to clinical outcome. The paper appears in the December issue of the Journal of the National Cancer Institute.
A multiplex image analyzed by AQUA to quantitatively analyze protein expression. Different colors represent compartments where protein concentration is measured; the number of pixels of each color is compared to the total number of pixels to give protein concentration.
The study, led by David L. Rimm, M.D., associate professor of pathology and member of the Yale Cancer Center, was designed to make sense of inconsistencies in traditional immunohistochemistry, a technique widely used for evaluating biomarker levels. The researchers evaluated levels of the common breast cancer biomarkers HER2, p53 and estrogen receptor (ER) to determine the importance of antibody standardization. They used a tissue microarray format containing specimens from 250 breast cancer patients with available long-term survival data.
“We found that the antibody concentration chosen by pathologists can dramatically affect and even reverse the apparent relationships between biomarker expression levels and patient outcomes,” said Rimm. “This work challenges the way pathologists have viewed immunohistochemistry, and points out that biomarker expression studies need further development and analysis.”
Janet Rettig Emanuel | EurekAlert!
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