Levels of free prostate-specific antigen (PSA) can be selectively measuredby heat treatment of serum: free/total-PSA ratios improve detection of prostate carcinoma

We studied a simple heat treatment method for measuring free prostate-speci fic antigen (PSA). Samples were incubated at 56, 58, and 60 degrees C for 5 , 15, 30, 45, and 60 min. Then, 1 ml samples were fractionated on a Sephacr yl S-200 gel filtration column to separate alpha 1-antichymotrypsin-complex ed PSA (ACT-PSA) and free PSA. Values of ACT-PSA decreased with increasing incubation temperature and time, whereas free-PSA remained relatively const ant. The optimal temperature and time for incubation were 58 degrees C and 30 min. Using free/total-PSA ratios, we were able to distinguish between be nign prostatic hyperplasia and prostate carcinoma in patients whose PSA was in the diagnostic 'grey zone', i.e. 4.1 to 10.0 ng/ml. Through receiver op erating characteristic curve analysis, the area under the curve increased f rom 0.675 to 0.871 when comparing the performance of total PSA to the free/ total-PSA ratio. Thus, clinical application of our present methodology may reduce the need to obtain prostatic biopsies in patients whose PSA level is within the diagnostic 'grey zone'. (C) 1999 Elsevier Science B.V. All righ ts reserved.