Cellular distribution and heterogeneity of PSA and PSMA expression in normal, hyperplasia and human prostate cancer

ABSTRACT

As promising targets for in vivo diagnostic, prognostic and therapeutic approaches, the distribution and staining pattern of prostate specific antigen [PSA] and prostate specific membrane antigen [PSMA] in tumors are of significant interest. To compare the cellular distribution and heterogeneity of PSA and PSMA expression in normal prostate [NP], benign prostatic hyperplasia [BPH] and primary prostatic tumors and to analyze their relation with the angiogenic activity according to Gleason grade [low, medium and high] in primary PC. The study was carried out in 6 NP, 44 BPH and 39 PC. Immunohistochemical analysis was performed. Monoclonal antibodies 3E6 and ER-PR8 were used to assess PSMA and PSA expression respectively. The evaluation of angiogenesis was made by CD34 immune marker. In our study we noticed differences in the intracellular localization of the PSMA immunostaining which seem to be related to the normal and pathological context. A significant number of primary tumors presented with apical pattern of PSMA [28/39]; whereas a relevant part of NP samples and BPH samples showed cytoplasmic localization [4/6 and 30/44, respectively] in luminal epithelial cells. Compared to PSMA, PSA was preferentially localized in cytoplasmic compartment in all type of prostate. A direct correlation between histological grade, PSMA expression and angiogenic activity could be demonstrated in primary PC. Simultaneous stains with PSA and PSMA in individual prostate tissue will greatly improve the detection rate and identify a high risk PC that could progress to metastatic phenotype. Our findings clearly support the feasibility but also direct the potential of PSMA-targeted in vivo therapeutic approaches in PC patients rather than PSA especially those with poorly differentiated adenocarcinoma