title: Heterogeneity of prostate-specific membrane antigen (PSMA) expression in prostate carcinoma with distant metastasis.
abstract: 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.
authors.affiliation: Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria. sebastian.mannweiler@meduni-graz.at
authors.forename: Sebastian
authors.initials: S
authors.lastname: Mannweiler
authors.forename: Peter
authors.initials: P
authors.lastname: Amersdorfer
authors.forename: Slave
authors.initials: S
authors.lastname: Trajanoski
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Terrett
authors.forename: David
authors.initials: D
authors.lastname: King
authors.forename: Gabor
authors.initials: G
authors.lastname: Mehes
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000378:metabolism*; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D000954:Antigens, Surface; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II