Cappuzzo F, Finocchiaro G, Rossi E, Jänne P A, Carnaghi C, Calandri C, Bencardino K, Ligorio C, Ciardiello F, Pressiani T, Destro A, Roncalli M, Crino L, Franklin W A, Santoro A, Varella-Garcia M
Department of Medical Oncology, Istituto Clinico Humanitas IRCCS, Rozzano, Italy.
Ann Oncol. 2008 Apr;19(4):717-23. doi: 10.1093/annonc/mdm492. Epub 2007 Oct 31.
Standardized conditions to distinguish subpopulations of colorectal cancer (CRC) patients more and less sensitive to cetuximab therapy remain undefined.
We retrospectively analyzed epidermal growth factor receptor (EGFR) copy number by fluorescence in situ hybridization (FISH) in paraffin-embedded tumor blocks from 85 chemorefractory CRC patients treated with cetuximab. Results were analyzed according to different score systems previously reported in colorectal and lung cancers. The primary end point of the study was identification of the EGFR FISH score that best associates with response rate (RR).
Using receiver operating characteristic (ROC) analysis, the cut-off that best discriminated responders versus nonresponders to cetuximab was a mean of 2.92 EGFR gene copies per cell. This model showed sensitivity of 58.6% [95% confidence interval (CI) = 47.1-70.1) and specificity of 93.3% (95% CI = 80.6-100). EGFR FISH-positive patients (N = 43, 50.6%) had significantly higher RR (P = 0.0001) and significantly longer time to disease progression (P = 0.02) than EGFR FISH negative (N = 42, 49.4%). Other scoring systems resulted less accurate in discriminating patients with the highest likelihood of response to cetuximab therapy.
CRC patients with high EGFR gene copy number have an increased likelihood to respond to cetuximab therapy. Prospective clinical trials with a careful standardization of assay conditions and pattern interpretation are urgently needed.
区分对西妥昔单抗治疗反应性高和低的结直肠癌（CRC）患者亚群的标准化条件仍未明确。
我们回顾性分析了85例接受西妥昔单抗治疗的化疗难治性CRC患者石蜡包埋肿瘤组织块中表皮生长因子受体（EGFR）的拷贝数，采用荧光原位杂交（FISH）技术。根据先前在结直肠癌和肺癌中报道的不同评分系统分析结果。本研究的主要终点是确定与反应率（RR）最相关的EGFR FISH评分。
采用受试者工作特征（ROC）分析，区分西妥昔单抗反应者与无反应者的最佳临界值是每个细胞平均2.92个EGFR基因拷贝。该模型显示敏感性为58.6%[95%置信区间（CI）=47.1-70.1]，特异性为93.3%（95%CI=80.6-100）。EGFR FISH阳性患者（N=43，50.6%）的RR显著更高（P=0.0001），疾病进展时间显著更长（P=0.02），而EGFR FISH阴性患者（N=42，49.4%）则不然。其他评分系统在区分对西妥昔单抗治疗反应可能性最高的患者方面准确性较低。
EGFR基因拷贝数高的CRC患者对西妥昔单抗治疗反应的可能性增加。迫切需要进行前瞻性临床试验，并仔细规范检测条件和结果解读模式。
