Prostate-specific membrane
antigen (PSMA) is a transmembrane
protein that is overexpressed in advanced stage prostate
adenocarcinomas. As a novel target for in vivo prognostic and therapeutic approaches, the distribution pattern of PSMA in primary and metastatic
tumors is of significant interest. In this study we addressed the cellular distribution and heterogeneity of PSMA expression.
Paraffin-embedded sections of 51 patients with primary prostate
carcinoma and distant
metastases were evaluated. Immunohistochemistry was used to determine the cellular localization, staining intensity and positive cell fraction which were related to
tumor type and growth pattern. We demonstrated differences in the intracellular localization of the PSMA immunostaining which seem to be related to the
tumor differentiation pattern. A significant number of the primary
tumors (7/51) and
metastases (6/51) presented with highly heterogeneous PSMA expression and in further 2 primary, and 8 metastatic
tumors the staining was in the negative range (<10% positive
tumor cells). A direct correlation between histological parameters and PSMA expression could not be demonstrated. Our findings clearly support the feasibility but also direct to potential failures of PSMA-targeted in vivo diagnostic and therapeutic approaches in
prostate cancer patients with distant
metastasis.