Progression of prostate cancer: Diagnostic and prognostic utility of prostate-specific antigen, alpha(2)-macroglobulin, and their complexes

We previously reported cases of advanced prostate cancer (PCa) in which ser um alpha (2)-macroglobulin (alpha M-2) levels were markedly decreased to le ss than approximately 50 mg/dl whereas serum prostate-specific antigen (PSA ) levels were remarkably increased. These cases were not complicated with d isseminated intravascular coagulation (DIC). In this study, we measured ser um PSA and alpha M-2 in 108 patients with either benign prostatic hyperplas ia (BPH) or PCa to elucidate the relationship between PSA, i.e. the serum p rotease derived from the prostatic tissue, and alpha M-2, i.e. the protease inhibitor that was the most abundantly contained in serum. alpha M-2 was d etermined by ELISA, total PSA and PSA-alpha (1)-antichymotrypsin (PSA-ACT) by EIA, and free-PSA by RIA in 44 patients with untreated BPH and 64 patien ts with untreated PCa. The ready association of alpha M-2 and PSA was asses sed using Western blotting to identify complexes of the two. Levels of tota l serum PSA correlated positively with those of PSA-ACT in PCa (r = 0.99, p < 0.001), and both levels increased with advancing stage of disease. In co ntrast, the serum-free PSA/total PSA ratio (free/total PSA) and <alpha>M-2 levels decreased as the disease progressed. However, only the free/total PS A ratio attained significant difference for localized cancer in stage T1,2 versus BPH (p < 0.05). In stage Mlb PCa, in which serum PSA levels were ver y high, there was a negative correlation between the total PSA and <alpha>M -2 values (r = -0.57, p < 0.05). In addition, serum <alpha>M-2 Levels tende d to decrease with progression of PCa. Serum total PSA levels correlated ti ghtly with serum PSA-ACT levels. It is suggested that PSA is usually comple xed with ACT in the serum. Free/total PSA was useful for differential diagn osis between early cancer and BPH. Levels of serum alpha M-2 of less than 5 0 mg/dl in PCa patients may indicate a possibility of bone metastases.