Shariat Shahrokh F, Bensalah Karim, Karam Jose A, Roehrborn Claus G, Gallina Andrea, Lotan Yair, Slawin Kevin M, Karakiewicz Pierre I
Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9110, USA.
Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5377-84. doi: 10.1158/1078-0432.CCR-07-0330.
Human epidermal growth factor receptor-2 (HER2) and epidermal growth factor receptor (EGFR) expression have been associated with disease progression in patients with prostate cancer. We tested the hypothesis that plasma levels of HER2 and/or EGFR are associated with prostate cancer stage and prognosis in patients with clinically localized disease.
We measured preoperative plasma HER2 and EGFR levels using commercially available ELISAs on banked plasma from 227 patients treated with radical prostatectomy and bilateral lymphadenectomy for clinically localized prostate adenocarcinoma.
Median preoperative plasma EGFR and HER2 levels were 31.4 ng/mL (interquartile range, 19.2 ng/mL) and 10.0 ng/mL (interquartile range, 2.7 ng/mL), respectively. HER2 was elevated in patients with seminal vesicle invasion (P = 0.033). In separate multivariate analyses that adjusted for the effects of standard preoperative predictors, lower EGFR, higher HER2, and higher HER2/EGFR ratio were associated with prostate-specific antigen (PSA) progression (P = 0.003, P < 0.001, and P < 0.001, respectively). In separate multivariate analyses that adjusted for the effects of standard postoperative predictors, lower EGFR and higher HER2/EGFR ratio were associated with PSA progression (P = 0.027 and P < 0.001, respectively). Among the patients who experienced PSA progression, HER2 was significantly higher (P = 0.023) and EGFR was lower (P = 0.04) in those with features of aggressive disease (i.e., development of metastasis, PSA doubling time <10 months, and/or failure to respond to local salvage radiation therapy).
Preoperative plasma HER2 and EGFR were associated with prostate cancer progression after radical prostatectomy. Plasma HER2 and EGFR may provide a tool for predicting long-term recurrence-free survival and early metastasis.
人表皮生长因子受体2（HER2）和表皮生长因子受体（EGFR）的表达与前列腺癌患者的疾病进展相关。我们检验了以下假设：HER2和/或EGFR的血浆水平与临床局限性疾病患者的前列腺癌分期及预后相关。
我们使用市售酶联免疫吸附测定法（ELISA），检测了227例因临床局限性前列腺腺癌接受根治性前列腺切除术和双侧淋巴结清扫术患者的术前血浆中HER2和EGFR水平，血浆样本均来自血库。
术前血浆EGFR和HER2水平的中位数分别为31.4 ng/mL（四分位间距，19.2 ng/mL）和10.0 ng/mL（四分位间距，2.7 ng/mL）。精囊侵犯患者的HER2水平升高（P = 0.033）。在分别针对标准术前预测因素影响进行校正的多因素分析中，较低的EGFR、较高的HER2以及较高的HER2/EGFR比值与前列腺特异性抗原（PSA）进展相关（分别为P = 0.003、P < 0.001和P < 0.001）。在分别针对标准术后预测因素影响进行校正的多因素分析中，较低的EGFR和较高的HER2/EGFR比值与PSA进展相关（分别为P = 0.027和P < 0.001）。在经历PSA进展的患者中，具有侵袭性疾病特征（即发生转移、PSA倍增时间<10个月和/或对局部挽救性放射治疗无反应）的患者HER2显著更高（P = 0.023），而EGFR更低（P = 0.04）。
术前血浆HER2和EGFR与根治性前列腺切除术后的前列腺癌进展相关。血浆HER2和EGFR可能为预测长期无复发生存和早期转移提供一种工具。
