Department of Medical Oncology, Regina Elena Institute, Rome, Italy.
J Transl Med. 2010 Apr 16;8:36. doi: 10.1186/1479-5876-8-36.
Responsiveness to Cetuximab alone can be mediated by an increase of Epidermal Growth factor Receptor (EGFR) Gene Copy Number (GCN). Aim of this study was to assess the role of EGFR-GCN in advanced colorectal cancer (CRC) patients receiving chemotherapy plus Cetuximab.
One hundred and one advanced CRC patients (43 untreated- and 58 pre-treated) were retrospectively studied by fluorescence in situ hybridization (FISH) to assess EGFR-GCN and by immunohistochemistry (IHC) to determine EGFR expression. Sixty-one out of 101 patients were evaluated also for k-ras status by direct sequencing. Clinical end-points were response rate (RR), progression-free survival (PFS) and overall survival (OS).
Increased EGFR-GCN was found in 60/101 (59%) tumor samples. There was no correlation between intensity of EGFR-IHC and EGFR-GCN (p = 0.43). Patients receiving chemotherapy plus Cetuximab as first line treatment had a RR of 70% (30/43) while it was 18% (10/56) in the group with previous lines of therapy (p < 0.0001). RR was observed in 29/60 (48%) of patients with increased EGFR-GCN and in 6/28 (21%) in those without (p = 0.02). At multivariate analyses, number of chemotherapy lines and increased EGFR-GCN were predictive of response; EGFR-IHC score, increased EGFR-GCN and number of chemotherapy lines were significantly associated with a significant better PFS. Response to therapy was the only prognostic predictive factor for OS. In the 60 patients analyzed for k-ras mutations, number of chemotherapy lines, increased EGFR-GCN and k-ras wild type status predicted a better PFS.
In metastatic CRC patients treated with chemotherapy plus Cetuximab number of chemotherapy lines and increased EGFR-GCN were significantly associated with a better clinical outcome, independent of k-ras status.
西妥昔单抗的反应性可能是由表皮生长因子受体（EGFR）基因拷贝数（GCN）增加介导的。本研究旨在评估 EGFR-GCN 在接受化疗联合西妥昔单抗治疗的晚期结直肠癌（CRC）患者中的作用。
通过荧光原位杂交（FISH）检测 101 例晚期 CRC 患者（43 例未经治疗和 58 例预处理）的 EGFR-GCN，并通过免疫组化（IHC）检测 EGFR 表达。61 例患者还通过直接测序评估 k-ras 状态。临床终点为反应率（RR）、无进展生存期（PFS）和总生存期（OS）。
在 101 例肿瘤样本中发现 60/101（59%）的 EGFR-GCN 增加。EGFR-IHC 强度与 EGFR-GCN 之间无相关性（p = 0.43）。接受化疗联合西妥昔单抗作为一线治疗的患者 RR 为 70%（30/43），而先前接受过治疗的患者 RR 为 18%（10/56）（p < 0.0001）。在 EGFR-GCN 增加的 60 例患者中观察到 RR，而在 EGFR-GCN 无增加的 28 例患者中观察到 6 例（p = 0.02）。多因素分析显示，化疗线数和 EGFR-GCN 增加是反应的预测因素；EGFR-IHC 评分、EGFR-GCN 增加和化疗线数与显著更好的 PFS 显著相关。对治疗的反应是 OS 的唯一预后预测因素。在分析 60 例 k-ras 突变的患者中，化疗线数、EGFR-GCN 增加和 k-ras 野生型状态预测 PFS 更好。
在接受化疗联合西妥昔单抗治疗的转移性 CRC 患者中，化疗线数和 EGFR-GCN 增加与更好的临床结局显著相关，与 k-ras 状态无关。
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