Italiano Antoine, Follana Philippe, Caroli François-Xavier, Badetti Jean-Luc, Benchimol Daniel, Garnier Georges, Gugenheim Jean, Haudebourg Juliette, Keslair Frédérique, Lesbats Gérard, Lledo Gérard, Roussel Jean-Francois, Pedeutour Florence, François Eric
Department of Medical Oncology, Centre Antoine-Lacassagne, Canceropôle PACA, Nice, France.
Ann Surg Oncol. 2008 Feb;15(2):649-54. doi: 10.1245/s10434-007-9667-2. Epub 2007 Nov 7.
EGFR (epidermal growth factor receptor) gene gain assessed by FISH (fluorescence in situ hybridization) has been shown to be predictive of response to EGFR-targeted therapies in patients with non-small cell lung cancer. The aim or our study was to relate the EGFR gene copy number to therapeutic results in patients with metastatic colorectal cancer (CRC) treated with a cetuximab-containing regimen.
Forty-seven patients with metastatic CRC treated with a cetuximab-containing regimen between August 2004 and September 2006 were included in our study. EGFR status was assessed by immunohistochemistry (IHC) and by FISH on fixed paraffin-embedded sections of tumor specimens.
By IHC (n = 47), 39 patients (83%) had EGFR-positive tumors. EGFR gene copy gain was detected in 8 (19.5%) of 41 tumors. Neither EGFR expression assessed by IHC nor EGFR gene copy gain assessed by FISH were statistically significantly correlated with objective response rate, disease control rate, progression-free survival, and overall survival. Of the 33 patients whose tumors were FISH negative, 8 patients (24.2%) had a partial response, and 10 (30.3%) had stable disease.
EGFR FISH analysis does not seem to be a sufficiently robust test for selecting candidate CRC patients for cetuximab therapy.
通过荧光原位杂交（FISH）评估的表皮生长因子受体（EGFR）基因扩增已被证明可预测非小细胞肺癌患者对EGFR靶向治疗的反应。我们研究的目的是将EGFR基因拷贝数与接受含西妥昔单抗方案治疗的转移性结直肠癌（CRC）患者的治疗结果相关联。
2004年8月至2006年9月期间接受含西妥昔单抗方案治疗的47例转移性CRC患者纳入我们的研究。通过免疫组织化学（IHC）和对肿瘤标本固定石蜡包埋切片进行FISH评估EGFR状态。
通过IHC（n = 47），39例患者（83%）肿瘤EGFR呈阳性。41例肿瘤中有8例（19.5%）检测到EGFR基因拷贝增加。通过IHC评估的EGFR表达和通过FISH评估的EGFR基因拷贝增加均与客观缓解率、疾病控制率、无进展生存期和总生存期无统计学显著相关性。在33例FISH阴性的患者中，8例（24.2%）有部分缓解，10例（30.3%）病情稳定。
EGFR FISH分析似乎不是选择西妥昔单抗治疗CRC候选患者的充分有力的检测方法。
