Cetuximab shows activity in colorectal cancer patients with tumors for which FISH analysis does not detect an increase in EGFR gene copy number
Cetuximab shows activity in colorectal cancer patients with tumors for which FISH analysis does not detect an increase in EGFR gene copy number
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DOI：
10.1245/s10434-007-9667-2
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发表时间：
2008-02-01
影响因子：
3.7
通讯作者：
Francois, Eric
中科院分区：
文献类型：
--
作者：
Italiano, Antoine;Follana, Philippe;Francois, Eric
背景：通过荧光原位杂交(FISH)评估EGFR(表皮生长因子受体)基因的获得，已被证明可以预测非小细胞肺癌患者对EGFR靶向治疗的反应。本研究旨在探讨含西妥昔单抗方案治疗的转移性结直肠癌(CRC)患者中EGFR基因拷贝数与疗效的关系。采用免疫组织化学(IHC)和荧光原位杂交(FISH)方法检测肿瘤标本中EGFR的表达情况。结果：47例患者中，39例(83%)肿瘤组织中有EGFR表达。41个肿瘤中有8个(19.5%)检测到EGFR基因拷贝增加。IHC评估的EGFR表达和FISH评估的EGFR基因复制增益与客观缓解率、疾病控制率、无进展生存期和总生存期均无统计学意义。在33例FISH阴性的患者中，8例(24.2%)部分缓解，10例(30.3%)病情稳定。结论：EGFR FISH分析不能作为筛选西妥昔单抗治疗候选结直肠癌患者的可靠方法。
Background: 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.Methods: 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.Results: 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.Conclusions: EGFR FISH analysis does not seem to be a sufficiently robust test for selecting candidate CRC patients for cetuximab therapy.