Nonhuman primates as models for studies of prostate specific antigen and prostatic diseases

Abstract

BACKGROUND Because prostate specific antigen (PSA) is released at increased levels into the blood early in the development of prostate cancer, benign prostatic hyperplasia (BPH) and prostatitis, it is widely used as a marker for these diseases. However, PSA has clinical limitations as a screen for prostatic diseases due to its low sensitivity and specificity. There is a strong need to better understand the biology of PSA and factors affecting its serum levels. METHODS We evaluated cynomolgus macaques, rhesus macaques, baboons, and marmosets for their suitability as models for the study of PSA biology and prostatic diseases. RESULTS Prostates of several nonhuman primates are anatomically similar to the human counterpart. Anti‐human PSA antibody detected PSA antigens in all the Old World monkeys (cynomolgus macaques, rhesus macaques, and baboons) but not in marmosets. Of the Old World monkeys, cynomolgus macaques have the highest serum PSA levels; baboons have the lowest. Serum PSA levels from macaques includes a number of outlier samples with unusually high values. We also report two cases of abnormal pathologies in macaques accompanied by high serum PSA levels. One case consisted of prostatic hyperplasia involving both glandular and basal cells in a cynomolgus macaque and another of glandular hyperplasia and atrophy in a rhesus macaque. The finding that pathological changes in the prostate of macaques may lead to increases in serum PSA is worthy of further exploration. CONCLUSION Cynomolgus macaques and rhesus macaques are promising animal models for PSA biology studies. Prostate 68: 1546–1554, 2008.