Early Overexpression of the Bombesin Receptor Type 2 in Prostatic Carcinogenesis
Meike Korner, Beatrice Waser, Ruth Rehmann, Jean Claude Reubi. Institute of Pathology of the University of Berne, Berne, Switzerland
Background: It is well known that the bombesin type 2 (BB2) receptor shows high over-expression in prostatic invasive adenocarcinoma and high grade PIN, but low expression in normal prostate glands. This represents the molecular basis for clinical applications, namely in vivo BB2 receptor imaging of metastatic prostate cancer with radioactive bombesin analogues. However, a focal, high density BB2 receptor expression can occasionally be observed in prostate glands which so far have not been histopathologically characterized.
Design: The prostatic BB2 receptor expression was quantitatively assessed with in vitro receptor autoradiography using 125I-[Tyr4]-bombesin in frozen tissue samples from 115 prostatectomy specimens. On successive tissue sections, BB2 receptor autoradiography was compared with H&E staining and MIB-1 and 34bE12 immunohistochemistry.
Results: Invasive adenocarcinoma and high grade PIN expressed BB2 receptors in high incidence (77% and 73%, respectively) and high density, while non-neoplastic prostate glands expressed BB2 receptors in 18% of cases in low density. Of particular interest was the frequent observation of focal non-invasive prostate glands with high BB2 receptor density. These glands were characterized by low grade nuclear atypia and increased proliferation, compatible with PIN of low degree. There was a marked BB2 receptor density gradient, increasing from normal prostate glands (mean relative optical density, ROD, of 125I-[Tyr4]-bombesin binding: 0.17) over focal atypical glands without increased MIB-1 expression (mean ROD: 0.28; p=0.005) and focal atypical glands with increased MIB-1 labelling (mean ROD: 0.44; p=0.002) to high grade PIN and invasive adenocarcinoma (mean ROD: 0.61; p=0.002).
Conclusions: BB2 receptor over-expression may be a novel, specific marker of early neoplastic transformation in the prostate, arising in low grade PIN and progressively increasing during malignant progression. These data may have important consequences for the interpretation of in vivo BB2 receptor imaging of prostate pathology.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 75, Tuesday Morning