BY GREG MILLER
The World Health Organization (WHO) has designated two calibration standards developed at Stanford as international standards to be used to improve the reliability of blood tests for prostate specific antigen (PSA), an important indicator of prostate cancer.
The Stanford calibrators are standardized samples of purified PSA that will be used by doctors around the world to calibrate the assays they use to determine blood levels of PSA. This calibration will help ensure that PSA tests done at different times or different places yield consistent results.
PSA is an enzyme produced by the healthy male prostate gland, explained Thomas Stamey, MD, professor of urology and head of the research team that developed the calibrators. However, in men with prostate cancer, levels of the enzyme increase because cancer cells also produce it. High levels of PSA in the blood, therefore, indicate an increased likelihood of cancer.
"In the United States, 80 percent of all men diagnosed with prostate cancer are diagnosed because of their PSA level," Stamey said.
As is the case for any diagnostic tool, though, PSA levels are only useful if the assays used to measure them are reliable.
When the first PSA assays became available in the late 1980s, Stamey said, there was no way to standardize assays made by different manufacturers. Tests in his laboratory during this time showed that different assays could give results that differed by as much as 100 percent for the same blood sample.
As a result PSA levels measured in the same patient at different times could vary substantially if different assays were used, even if the patient's actual PSA levels did not change. Stamey and his colleagues tackled this problem by working to produce purified samples of PSA that could be used to calibrate the assays and eliminate major discrepancies among different brands.
Their task was complicated because PSA comes in two forms, termed "free" and "complexed." In men with prostate cancer, 90 percent of the PSA in the blood is in the complexed form. This percentage is lower in men without cancer, including men with a common but harmless enlargement of the prostate called benign prostatic hyperplasia (BPH).
As a result, the makeup of the PSA in the blood, in addition to the overall PSA level, provides important information. Men with elevated total PSA levels and a high percentage of complexed PSA are more likely to have cancer than men whose PSA levels are elevated by an increase in the free form of PSA -- a condition indicative of BPH.
The makeup of the PSA in the blood is typically determined by running two assays -- one to measure the free PSA level and one to measure the total (free plus complexed) PSA level. Therefore, two calibrators were needed -- one for each assay.
Stamey's group developed the two calibrators and presented them to the National Committee for Clinical Laboratory Standards, the official body that approves laboratory assays in the United States. The calibrators were approved as the U.S. national standard in 1997.
The same year, Stamey was notified that the calibrators were among several candidates under consideration by WHO for use as worldwide standards. Each standard underwent extensive evaluation, which included testing the stability of the samples and their ability to withstand temperature variations that might be encountered around the world.
The announcement that the Stanford
standards had been chosen was made last month in Geneva,
Switzerland at the 50th meeting of WHO's Expert Committee on
Biological Standardization. SR