Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, Department of Urology, Cancer and Haematology Centre, The Churchill Hospital, Old Road, Headington, Oxford, UK.
BJU Int. 2011 May;107(9):1488-99. doi: 10.1111/j.1464-410X.2010.09556.x. Epub 2010 Sep 14.
• To compare immunostaining protocols using different antibodies for the type 1 insulin-like growth factor receptor (IGF-1R) in channel transurethal resection of the prostate (chTURP) chips, and to investigate how IGF-1R expression varies with time in serial prostate cancer specimens from individual patients.
• We studied IGF-1R expression in 44 prostate cancer specimens from 18 patients who had undergone serial chTURP at least 3 months apart. • Retrospective analysis of the hospital notes was undertaken to obtain clinical information, including age, Gleason score, prostate-specific antigen (PSA) level, hormone treatment and metastatic disease status at the time of each operation. • After an optimization process using three commercially-available IGF-1R antibodies, we used two antibodies for semiquantititve immunostaining of serial chTURP chips.
• Santa Cruz antibody sc713 gave positive staining in IGF-1R null R- cells, and was not used further. Antibodies from Cell Signaling Technology (Beverly, MA, USA) (CS) and NeoMarkers Inc. (Fremont, CA, USA) (NM) did not stain R- cells and, in prostate tissue, showed staining of the glandular epithelium, with negligible stromal staining. All 44 chTURP samples contained identifiable malignant tissue and, of these, 73% and 64% scored moderately or strongly (score 3 or 4) with the CS and NM antibodies respectively. • There was significant correlation of IGF-1R scores of malignant tissue between the two antibodies (P < 0.001). By contrast, staining of benign glands showed poor correlation between antibodies: CS gave significantly weaker staining than malignant epithelium in the same sections (P < 0.001), whereas NM showed poor discrimination between malignant and benign glands. IGF-1R staining scores generated by the CS antibody were used to analyze the clinical data. • Most patients (six of seven) with falling IGF-1R staining scores were responding to androgen deprivation therapy (confirmed by PSA response) between operations. Conversely, in seven of eight patients who had progression to androgen-independence between procedures, IGF-1R levels increased or remained high. Finally, seven of 11 patients who developed radiologically confirmed metastases between procedures showed stable or increasing IGF-1R staining scores.
• The present study is the first to assess changes in IGF-1R expression in serial prostate cancer samples. The results obtained indicate that IGF-1R expression usually remains high throughout the course of histologically-proven disease progression in serial specimens, suggesting that the IGF-1R remains a valid treatment target for advanced prostate cancer.
比较使用不同抗体对 1 型胰岛素样生长因子受体（IGF-1R）进行免疫染色的方案，研究在个体患者的连续前列腺癌标本中 IGF-1R 表达随时间的变化。
我们研究了 18 名至少相隔 3 个月接受连续经尿道前列腺电切术（chTURP）的患者的 44 份前列腺癌标本中的 IGF-1R 表达。对医院记录进行回顾性分析，以获取临床信息，包括年龄、Gleason 评分、前列腺特异性抗原（PSA）水平、激素治疗和每次手术时的转移性疾病状态。在使用三种市售 IGF-1R 抗体进行优化过程后，我们使用两种抗体对半定量免疫染色连续 chTURP 芯片。
Santa Cruz 抗体 sc713 在 IGF-1R 阴性 R-细胞中呈阳性染色，因此不再进一步使用。来自 Cell Signaling Technology（马萨诸塞州 Beverly）的抗体（CS）和 NeoMarkers Inc.（加利福尼亚州 Fremont）的抗体（NM）均未染色 R-细胞，在前列腺组织中，仅染色腺体上皮，几乎没有间质染色。所有 44 个 chTURP 样本均包含可识别的恶性组织，其中 73%和 64%分别用 CS 和 NM 抗体中度或强烈（评分 3 或 4）染色。两种抗体之间恶性组织的 IGF-1R 评分具有显著相关性（P < 0.001）。相比之下，良性腺体的染色相关性较差：CS 在相同切片中对恶性上皮的染色明显弱于良性腺体（P < 0.001），而 NM 对恶性和良性腺体的区分较差。使用 CS 抗体生成的 IGF-1R 染色评分用于分析临床数据。大多数（七分之六）IGF-1R 染色评分下降的患者在手术之间接受雄激素剥夺治疗时（通过 PSA 反应证实）有反应。相反，在手术之间进展为雄激素非依赖性的八名患者中，IGF-1R 水平升高或保持较高水平。最后，在手术之间出现放射学证实转移的 11 名患者中，有 7 名患者的 IGF-1R 染色评分稳定或升高。
本研究首次评估了连续前列腺癌样本中 IGF-1R 表达的变化。结果表明，在连续标本中，IGF-1R 表达通常在组织学证实的疾病进展过程中保持较高水平，这表明 IGF-1R 仍然是晚期前列腺癌的有效治疗靶点。
