Institute of Clinical Pathology, University Hospital of Zürich, Zürich, Switzerland.
Prostate. 2012 Feb;72(3):318-25. doi: 10.1002/pros.21434. Epub 2011 Jul 7.
The gastrin-releasing peptide receptor (GRPR) has emerged as an attractive target for both therapeutic and diagnostic appliances, but has only insufficiently been characterized in the human prostate so far. The aim of this study is to profile GRPR in a large cohort and correlate it with clinicopathologic and molecular parameters.
Benign and malignant (primary carcinoma, metastases, and castration-resistant prostate cancer) prostate samples from 530 patients were analyzed immunohistochemically for GRPR, androgen receptor and Cyclin D1 expression. Staining intensity was assessed assigning a semiquantitative score to each sample.
Normal prostate tissues were mostly GRPR negative, significantly higher expression rates were seen in primary carcinomas and metastases. Significant inverse correlations were found for GRPR and increasing Gleason score, PSA value, and tumor size. A stratified Kaplan-Meyer analysis for GRPR and high AR expression shows a significant prognostic advantage for high GRPR expression, whereas GRPR expression alone shows no independent prognostic value. Highly significant correlations for GRPR, AR, and Cyclin D1 were found.
Our data show that GRPR is overexpressed in prostate cancer, particularly of lower grade and smaller size. These findings constitute a caveat for the use of GRPR as a target for diagnostic or therapeutic approaches to high grade or progressed prostate cancer.
胃泌素释放肽受体（GRPR）已成为治疗和诊断应用的有吸引力的靶点，但迄今为止在人类前列腺中的特征仅不足够。本研究的目的是在大样本中分析 GRPR，并将其与临床病理和分子参数相关联。
对 530 例患者的良性和恶性（原发性癌、转移和去势抵抗性前列腺癌）前列腺样本进行免疫组织化学分析，以检测 GRPR、雄激素受体和 Cyclin D1 的表达。对每个样本进行半定量评分，评估染色强度。
正常前列腺组织大多为 GRPR 阴性，原发性癌和转移瘤中的表达率显著更高。GRPR 与逐渐增加的 Gleason 评分、PSA 值和肿瘤大小呈显著负相关。对 GRPR 和高 AR 表达进行分层 Kaplan-Meier 分析显示，高 GRPR 表达具有显著的预后优势，而单独的 GRPR 表达则没有独立的预后价值。还发现了 GRPR、AR 和 Cyclin D1 之间的高度显著相关性。
我们的数据表明，GRPR 在前列腺癌中过度表达，特别是低级别和较小的肿瘤。这些发现为将 GRPR 用作诊断或治疗高等级或进展性前列腺癌的靶点提供了警示。
