Steve Bogen, MD, PhD, is a board-certified clinical pathologist, who graduated from the University of Chicago Pritzker School of Medicine (MD) and the Weizman Institute of Science (PhD), with a post-graduate residency and research fellowship at the Brigham and Women’s Hospital. He is adjunct professor of pathology and laboratory medicine at Tufts University School of Medicine and, until recently, was medical director, clinical chemistry laboratory at Tufts Medical Center. Dr. Bogen is an inventor on 22 patents, all of which relate to various medical diagnostic technologies. In addition, he served for a decade on several NIH grant review committees. Dr. Bogen was previously the founder of CytoLogix Corporation, which developed the Artisan® instrument system for automated complex histopathology stains (now sold and supported by Agilent Corporation).
In laboratory medicine, improved test accuracy and reproducibility leads to profound changes that benefit millions of people. For example, every diabetic is familiar with the hemoglobin A1c test. However, the average diabetic is likely unaware that standardizing the test was a formidable challenge, delaying its adoption as a diagnostic criterion for diabetes. The efforts of laboratory professionals to fix the problem were pivotal in the lives of so many.
Today, blood samples are analyzed by any lab in the country and the results are essentially the same, whether that lab is in Boston or Beverly Hills. We, as laboratory professionals, take that for granted but it wasn’t always the case. Precise and accurate testing is the result of clinical pathology labs adopting assay calibrators traceable to agreed-upon international reference standards that ensure every laboratory uses the same system of measurement. In fields such as clinical chemistry, immunology, and hematology, the rate of analytic laboratory errors is less than 1 percent; thus, physicians are confident in the results they provide to patients.
The testing reality is starkly different in immunohistochemistry (IHC), a test format widely used in surgical pathology to evaluate cancers in tissue samples and determine correct treatment. IHC lacks reference standards, assay calibration is nonexistent and, until now, the technology for incorporating traceable units of measure to standardize IHC assays was unattainable.
IHC is almost always a qualitative test format; the test result is positive or negative. Just by guessing, you would have a 50/50 chance of delivering the correct test result. The overwhelming consensus of published data show that by performing IHC testing and not guessing, we only increase the rate of accurate test results from 50 percent to 70–90 percent. In other words, the error rates in IHC are at least 10 times those of blood testing laboratories.
The implications of IHC test variability are huge for cancer patients, prescribing physicians, pathologists, and clinical lab managers. Lab-to-lab variation leads to false positive or false negative results, meaning patients are potentially misdiagnosed and/or receive the wrong treatment, or need to be retested.
Analytic reference standards, calibrators, and traceable units of measure to produce consistent and accurate results are essential to remedying this problem.
Recognizing this compelling need, the National Cancer Institute funded the newly formed Consortium for Analytic Standardization in Immunohistochemistry (CASI). Launched earlier this month, this new organization is led by an international panel of pathologists and scientists and is dedicated to improving patient IHC test accuracy and reproducibility.
As principal investigator of the project, I’m proud to serve on the steering committee and energized by the vital work ahead. CASI will conduct studies to determine appropriate analytic sensitivity thresholds for selected IHC tests, publish the data it collects, and then offer analytic sensitivity recommendations. In addition to guiding routine clinical practice, these recommendations will facilitate and simplify methodology transfer between laboratories, from published literature, and in clinical trials.
Ultimately, my hope is that someday, laboratory professionals are able to say about IHC what is said for hemoglobin A1c testing: The increased accuracy and reproducibility of IHC has dramatically improved the lives of millions of cancer patients.