Okegawa Takatsugu, Kinjo Manami, Nutahara Kikuo, Higashihara Eiji
Department of Urology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Int J Urol. 2006 Sep;13(9):1197-201. doi: 10.1111/j.1442-2042.2006.01533.x.
Overexpression of the HER2 receptor protein and amplification of the HER2 gene has been implicated in tumor development and progression, and has been associated with a poor prognosis in several types of cancer. The aim of this study was to evaluate whether pretreatment serum HER2 levels can be used to predict biochemical recurrence-free survival in prostate cancer patients about to undergo endocrine therapy.
The study population consisted of 379 untreated patients with histologically diagnosed prostate cancer: 197 with T2N0M0, 93 with T3N0M0, 19 with TxN1Mx, and 70 with TxNxM1. Serum HER2 levels were assessed in the prostate cancer patients prior to treatment as well as in a control group of 100 patients with histologically confirmed non-cancer. Biochemical recurrence-free curves for the patients were investigated separately using the Kaplan-Meier method.
The mean level of HER2 in serum was significantly higher in prostate cancer patients than non-prostate cancer patients (P = 0.006). Also, the serum HER2 level was significantly higher in bone metastatic cancer patients (14.3 +/- 6.3 ng/mL) than in non-metastatic patients (T2: 11.9 +/- 2.3 ng/mL, P = 0.003; T3: 12.2 +/- 2.8 ng/mL, P = 0.011). The metastatic patients were divided into those with low and high HER2 levels using a cutoff value of 12.6 ng/mL based on receiver-operating characteristic curves. The biochemical recurrence-free rate was significantly poorer in patients with a high HER2 level (P = 0.0078, log-rank test). Multivariate Cox logistic regression analysis demonstrated that the pretreatment serum HER2 value (P = 0.022), serum prostate-specific antigen value (P = 0.018), and extent of disease score (P = 0.027) were independent predictors of recurrence.
The pretreatment serum HER2 level may be a useful independent prognostic factor that is associated with a high risk of biochemical recurrence in metastatic prostate cancer patients about to undergo endocrine therapy.
HER2受体蛋白的过表达和HER2基因的扩增与肿瘤的发生和发展有关，并且与几种癌症的预后不良相关。本研究的目的是评估治疗前血清HER2水平是否可用于预测即将接受内分泌治疗的前列腺癌患者的无生化复发生存期。
研究人群包括379例未经治疗且经组织学诊断为前列腺癌的患者：197例T2N0M0期、93例T3N0M0期、19例TxN1Mx期和70例TxNxM1期。在前列腺癌患者治疗前以及100例经组织学确诊为非癌症的对照组患者中评估血清HER2水平。使用Kaplan-Meier方法分别研究患者的无生化复发曲线。
前列腺癌患者血清中HER2的平均水平显著高于非前列腺癌患者（P = 0.006）。此外，骨转移癌患者的血清HER2水平（14.3±6.3 ng/mL）显著高于非转移患者（T2期：11.9±2.3 ng/mL，P = 0.003；T3期：12.2±2.8 ng/mL，P = 0.011）。根据受试者工作特征曲线，以12.6 ng/mL为临界值将转移患者分为HER2水平低和高的两组。HER2水平高的患者无生化复发率显著较差（P = 0.0078，对数秩检验）。多因素Cox逻辑回归分析表明，治疗前血清HER2值（P = 0.022）、血清前列腺特异性抗原值（P = 0.018）和疾病分期评分（P = 0.027）是复发的独立预测因素。
治疗前血清HER2水平可能是一个有用的独立预后因素，与即将接受内分泌治疗的转移性前列腺癌患者生化复发的高风险相关。
