Serum HER2 extracellular domain predicts an aggressive clinical outcome and biological PSA response in hormone-independent prostate cancer patients treated with docetaxel
Serum HER2 extracellular domain predicts an aggressive clinical outcome and biological PSA response in hormone-independent prostate cancer patients treated with docetaxel
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DOI：
10.1093/annonc/mdm490
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发表时间：
2008-02-01
影响因子：
50.5
通讯作者：
Mellado, B.
中科院分区：
文献类型：
--
作者：
Domingo-Domenech, J.;Fernandez, P. L.;Mellado, B.
背景：人类表皮生长因子受体2 （HER2）过表达与激素非依赖型前列腺癌（HIPC）进展有关。其临床价值及与治疗的相关性尚不明确。患者和方法：通过免疫分析前瞻性检测多西他赛（泰索帝）治疗的HIPC患者血清HER2细胞外结构域（ECD）。采用免疫组织化学和荧光原位杂交法（FISH）检测肿瘤样品中的HER2。结果：纳入69例患者。24例（34.8%）患者HER2 ECD高（bbb15 ng/ml）。低HER2 ECD患者的PSA应答率为58%，高HER2 ECD患者的PSA应答率为36% （P = 0.046）。HER2 ECD水平是PSA进展时间的独立预后因素[危险比（HR） 2.82；95%置信区间（CI） 1.22 ~ 6.50；总生存率（HR 3.24; 95% CI 1.38 ~ 7.59; P = 0.007）。对17例患者的组织样本进行了HER2检测。HER2组织表达阴性的患者HER2 ECD水平较低（中位数为10.5 +/- 2.7 vs 30.5 +/- 24.8 ng/ml; P = 0.016）。所有样本FISH均为阴性。结论：高血清HER2 ECD水平与多西他赛治疗的HIPC患者的最差临床结果相关。
Background: Human epidermal growth factor receptor 2 (HER2) overexpression has been linked to hormone-independent prostate cancer (HIPC) progression. Its clinical value and correlation with therapy is not defined.Patients and methods: Patients with HIPC treated with docetaxel (Taxotere) were prospectively tested for serum HER2 extracellular domain (ECD) by immunoanalysis. HER2 was determined by immunohistochemistry and fluorescence in situ hybridization (FISH) in tumor samples.Results: Sixty-nine patients were included. Twenty-four (34.8%) patients had high HER2 ECD (>1 5 ng/ml). Prostate-specific antigen (PSA) response was 58% for patients with low HER2 ECD and 36% for patients with high HER2 ECD (P = 0.046). HER2 ECD levels were an independent prognostic factor for time to PSA progression [hazard ratio (HR) 2.82; 95% confidence interval (CI) 1.22-6.50; P = 0.015] and overall survival (HR 3.24; 95% CI 1.38-7.59; P = 0.007). Tissue samples from 17 patients were tested for HER2. Patients with negative HER2 tissue expression had lower HER2 ECD levels (median 10.5 +/- 2.7 versus 30.5 +/- 24.8 ng/ml; P = 0.016). FISH was negative in all samples.Conclusions: High HER2 ECD levels in serum are associated with a worst clinical outcome of HIPC patients treated with docetaxel.