EVALUATION OF PAP AND PSA GENE-EXPRESSION IN PROSTATIC HYPERPLASIA AND PROSTATIC-CARCINOMA USING NORTHERN-BLOT ANALYSES, IN-SITU HYBRIDIZATION AND IMMUNOHISTOCHEMICAL STAININGS WITH MONOCLONAL AND BISPECIFIC ANTIBODIES

In this report we have investigated levels of prostatic acid phosphata se (PAP) and prostate-specific antigen (PSA) gene expression in prosta tic carcinoma (Ca) and benign prostatic hyperplasia (BPH) specimens. N orthern-blot analyses of total prostatic mRNA indicated that there was a tendency towards lower amounts of PAP mRNA and PSA mRNA in the Ca s pecimens than in the BPH specimens, although, because of the great var iation in the expression levels of both mRNAs, these differences were not statistically significant. In situ hybridization analyses clearly showed that both PAP and PSA mRNAs were confined to the columnar epith elial cells and that stromal cells were devoid of these mRNAs. In addi tion, PAP and PSA mRNAs were more abundant in BPH tissue than in adjac ent Ca tissue within the same specimen. The levels of PAP and PSA enzy mes were analyzed immunohistochemically using a bispecific antibody ha ving high affinity for both PAP and PSA, and the results were compared with those obtained using monoclonal anti-PAP and anti-PSA antibodies . All 3 antibodies stained only epithelial cells and BPH tissue consis tently gave more intense staining than Ca tissue. Furthermore, the ant i-PSA and the bispecific anti-PAP-PSA antibodies stained well or moder ately differentiated Ca tissues more strongly than poorly differentiat ed Ca tissues. No PSA staining was detected in 3 and no PAP staining i n S of the moderately or poorly differentiated carcinomas (grades II o r III). Our results show that, in comparison with BPH tissue, prostati c Ca tissue is associated with significantly lower levels of mRNAs cod ing for the prostatic marker enzymes PAP and PSA, as well as with lowe r concentrations of these enzymes. Furthermore, dedifferentiation of p rostate Ca is associated with a decrease in the level of intraprostati c PSA. (C) 1993 Wiley-Liss, Inc.