title: Early over-expression of GRP receptors in prostatic carcinogenesis.
abstract: BACKGROUND
  The GRP receptor shows high over-expression in prostatic adenocarcinoma and high grade PIN, but low expression in normal prostate glands. This represents the molecular basis for GRP receptor imaging of prostate cancer with radioactive compounds. However, a focal, high density GRP receptor expression can be observed in hitherto uncharacterized prostate glands.
  
  
  METHODS
  GRP receptors were quantitatively measured with in vitro receptor autoradiography using ¹²⁵I-Tyr⁴ -bombesin in samples from 115 prostates. On successive tissue sections, ¹²⁵I-Tyr⁴ -bombesin autoradiography was compared with H&E staining and MIB-1 and 34βE12 immunohistochemistry.
  
  
  RESULTS
  On one hand, it was confirmed that GRP receptors were expressed in adenocarcinoma and high grade PIN in high density and high incidence (77% and 73%, respectively), but in normal prostate glands in low density and low frequency (18%). On the other hand, a novel and intriguing observation was the existence of focal non-invasive prostate glands with high GRP receptor density, characterized by low grade nuclear atypia and increased proliferation, compatible with lower grade PIN. There was a significant GRP receptor density gradient (P ≤ 0.005), increasing from normal prostate glands (mean relative optical density, ROD, of ¹²⁵I-Tyr⁴ -bombesin binding: 0.17) over atypical glands without increased MIB-1 labeling (0.28) and atypical glands with increased MIB-1 expression (0.44) to high grade PIN and adenocarcinoma (0.64 and 0.58, respectively).
  
  
  CONCLUSIONS
  GRP receptor over-expression may be a novel, specific marker of early prostatic neoplastic transformation, arising in low grade PIN, and progressively increasing during malignant progression. This should be considered when interpreting in vivo GRP receptor imaging in males.
authors.affiliation: Division of Cell Biology and Experimental Cancer Research, Institute of Pathology of the University of Berne, Berne, Switzerland.
authors.forename: Meike
authors.initials: M
authors.lastname: Körner
authors.forename: Beatrice
authors.initials: B
authors.lastname: Waser
authors.forename: Ruth
authors.initials: R
authors.lastname: Rehmann
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Reubi
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D001345:Autoradiography; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008297:Male; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D018004:Receptors, Bombesin / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D007457:Iodine Radioisotopes; C440408:MIB-1 antibody; D018004:Receptors, Bombesin
keywords: GRP receptor; bombesin receptor; in vitro receptor autoradiography; prostate cancer; prostatic intraepithelial neoplasia