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Comparison of Commercially Available Prostate-specific Antigen Samples by Mass Spectrometry

Mary B. Satterfield, Chad P. Nelson, David M. Bunk and Michael J. Welch

Analytical Chemistry Division, Chemical Sciences and Technology Laboratory, National Institute of Standards and Technology, Gaithersburg, Maryland 20899-8392

Prostate-specific antigen, PSA, is a single chain glycoprotein containing 237 amino acids that is widely used as a marker for prostate cancer.  Although found primarily in prostate and seminal fluid, low levels of PSA are also found in blood.  Blood serum levels of 4.0 ng/ml and below are generally considered normal; levels above 4.0 ng/ml typically trigger further testing including biopsies.  Several manufacturers have developed immunoaffinity tests for free PSA and for the predominant form of PSA: the PSA-antichymotrypsin (ACT) complex.  Unfortunately, comparisons of the tests reveal unacceptably high differences due to the heterogeneity of the PSA samples and differences in what is actually being measured by each test.  Work is ongoing at NIST to investigate the differences between the various commercial sources of PSA pursuant to possible selection of a PSA Standard Reference Material (SRM).  Once a PSA SRM is available, both the accuracy and precision of PSA tests performed by different methods should improve.  Development of a reference method for serum PSA will also be possible.

Samples of PSA from several different commercial producers of PSA have been analyzed by liquid chromatography electrospray ionization mass spectrometry (LC ESI MS) and matrix-assisted laser desorption mass spectrometry (MALDI).  The components of each sample, their stability over time and differences between lot numbers from the same source have been investigated.  Differences in the samples have been identified as due to sample degradation and differential glycosylation.  Selection criteria for choosing a Standard Reference Material will be discussed.