Division of Cell Biology and Experimental Cancer Research, Institute of Pathology of the University of Berne, Berne, Switzerland.
Prostate. 2014 Feb;74(2):217-24. doi: 10.1002/pros.22743. Epub 2013 Oct 22.
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.
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.
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).
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.
GRP 受体在前列腺腺癌和高级别 PIN 中高度过表达，但在正常前列腺中低表达。这代表了用放射性化合物对前列腺癌进行 GRP 受体成像的分子基础。然而，在迄今为止尚未描述的前列腺中可以观察到焦点、高密度的 GRP 受体表达。
使用¹²⁵I-Tyr⁴ - bombesin 通过体外受体放射自显影术，对 115 例前列腺样本中的 GRP 受体进行定量测量。在连续的组织切片上，将¹²⁵I-Tyr⁴ - bombesin 放射自显影与 H&E 染色以及 MIB-1 和 34βE12 免疫组织化学进行比较。
一方面，证实 GRP 受体在高浓度和高发生率（分别为 77%和 73%）的腺癌和高级别 PIN 中表达高密度，但在低密度和低频率（18%）的正常前列腺中表达。另一方面，存在具有高 GRP 受体密度的局灶性非侵入性前列腺腺的新的有趣观察结果，其特征为核异型性低度和增殖增加，与低级别 PIN 一致。GRP 受体密度存在显著的梯度（P≤0.005），从正常前列腺腺体（¹²⁵I-Tyr⁴ - bombesin 结合的相对光密度[ROD]均值为 0.17）逐渐增加，经过无 MIB-1 标记增加的非典型腺体（0.28）和 MIB-1 表达增加的非典型腺体（0.44），到高级别 PIN 和腺癌（分别为 0.64 和 0.58）。
GRP 受体过表达可能是前列腺早期肿瘤转化的一种新的、特异性标志物，起源于低级别 PIN，并在恶性进展过程中逐渐增加。在解释男性体内 GRP 受体成像时应考虑这一点。
