title: PSMA expression is highly homogenous in primary prostate cancer.
abstract: BACKGROUND
  Prostate-specific membrane antigen (PSMA) is a suggested target for antibody-based therapy of prostate cancer, potentially involved in the regulation of cell migration. As heterogeneity may limit the applicability of targeted therapies, this study was undertaken to estimate the degree of heterogeneity of PSMA expression in prostate cancer.
  
  
  METHODS
  For heterogeneity analysis, a prostate cancer heterogeneity TMA containing samples from 10 different tumor blocks of 189 consecutive prostate cancers was used. PSMA expression was analyzed by immunohistochemistry.
  
  
  RESULTS
  PSMA expression was found in 97.6% of 1171 interpretable tissue spots including 260 (22.2%) with weak, 345 (29.5%) with moderate, and 538 (45.9%) with strong positivity. On a patient level, a positive PSMA immunostaining was found in 172 of 173 analyzable patients (99.4%) with at least a weak staining reaction. PSMA immunostaining was homogenously positive in 161 prostate cancers (93.6%), whereas heterogenous PSMA positivity was seen in 11 of 172 positive cases (6.4%). In these cases, heterogeneity was intrafocal in 8 cases (72.7%) and interfocal in 27.3% cases. PSMA expression was completely absent in 1 patient.
  
  
  CONCLUSIONS
  Given the high frequency and high homogeneity of PSMA expression in prostate cancer, we conclude that increased PSMA expression may occur early in prostate cancer development. High homogeneity of PSMA expression is a strong argument for a high utility of PSMA as a prostate cancer drug target.
authors.affiliation: *Institute of Pathology †Martini-Clinic, Prostate Cancer Center ‡Department of Urology, Section for Translational Prostate Cancer Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Tsourlakis
authors.forename: Franka
authors.initials: F
authors.lastname: Klein
authors.forename: Martina
authors.initials: M
authors.lastname: Kluth
authors.forename: Alexander
authors.initials: A
authors.lastname: Quaas
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.forename: Alexander
authors.initials: A
authors.lastname: Haese
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000368:Aged; D000954:Antigens, Surface / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D018740:Genetic Heterogeneity; D043425:Glutamate Carboxypeptidase II / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016612:Paraffin Embedding; D011467:Prostate / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016707:Tissue Fixation
chemical_list: D000954:Antigens, Surface; D014408:Biomarkers, Tumor; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II