Epidermal Growth Factor Receptor (EGFR) gene copy number (GCN) correlates with clinical activity of irinotecan-cetuximab in K-RAS wild-type colorectal cancer: a fluorescence in situ (FISH) and chromogenic in situ hybridization (CISH) analysis.
Epidermal Growth Factor Receptor (EGFR) gene copy number (GCN) correlates with clinical activity of irinotecan-cetuximab in K-RAS wild-type colorectal cancer: a fluorescence in situ (FISH) and chromogenic in situ hybridization (CISH) analysis.
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DOI：
10.1186/1471-2407-9-303
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发表时间：
2009-08-27
期刊：
影响因子：
3.8
通讯作者：
Cascinu S
中科院分区：
文献类型：
--
作者：
Scartozzi M;Bearzi I;Mandolesi A;Pierantoni C;Loupakis F;Zaniboni A;Negri F;Quadri A;Zorzi F;Galizia E;Berardi R;Biscotti T;Labianca R;Masi G;Falcone A;Cascinu S
K-RAS野生型结直肠肿瘤显示对抗EGFR单克隆抗体的应答率提高。然而，70%至40%的患者似乎仍然没有从这种治疗方法中获益。FISH EGFR GCN先前已被证明与用抗EGFR单克隆抗体治疗的结直肠癌的临床结果相关。CISH似乎也能够提供准确的EGFR GCN信息，其优点是免疫组织化学和光学显微镜技术更简单，可重复性更强。基于这些发现，我们研究了FISH和CISH EGFR GCN与伊立替康-西妥昔单抗治疗的K-RAS野生型结直肠癌的临床结局之间的相关性。在基于伊立替康的化疗失败后接受伊立替康-西妥昔单抗治疗的晚期K-RAS野生型结直肠癌患者符合入选条件。从ROC曲线分析得出FISH和CISH的EGFR GCN的截止值分别为2.6和2.12。44例患者可用于分析。我们观察到FISH EGFR GCN ≥ 2.6和< 2.6的病例分别有9例（60%）和2例（9%）部分缓解（p = 0.002），CISH EGFR GCN ≥ 2.12和< 2.12的病例分别有10例（36%）和1例（6%）部分缓解（p = 0.03）。FISH和CISH EGFR GCN增加的患者中位TTP分别为7.7和6.4个月，而FISH和CISH EGFR GCN较低的患者中位TTP分别为2.9和3.1个月（分别为p = 0.04和0.02）。FISH和CISH EGFR GCN可能都是进一步选择接受西妥昔单抗治疗的K-RAS野生型结直肠癌患者的有效工具。
K-RAS wild type colorectal tumors show an improved response rate to anti-EGFR monoclonal antibodies. Nevertheless 70% to 40% of these patients still does not seem to benefit from this therapeutic approach. FISH EGFR GCN has been previously demonstrated to correlate with clinical outcome of colorectal cancer treated with anti-EGFR monoclonal antibodies. CISH also seemed able to provide accurate EGFR GCN information with the advantage of a simpler and reproducible technique involving immunohistochemistry and light microscopy. Based on these findings we investigated the correlation between both FISH and CISH EGFR GCN and clinical outcome in K-RAS wild-type colorectal cancer treated with irinotecan-cetuximab. Patients with advanced K-RAS wild-type, colorectal cancer receiving irinotecan-cetuximab after failure of irinotecan-based chemotherapy were eligible. A cut-off value for EGFR GCN of 2.6 and 2.12 for FISH and CISH respectively was derived from ROC curve analysis. Forty-four patients were available for analysis. We observed a partial remission in 9 (60%) and 2 (9%) cases with a FISH EGFR GCN ≥ 2.6 and < 2.6 respectively (p = 0.002) and in 10 (36%) and 1 (6%) cases with a CISH EGFR GCN ≥ 2.12 and < 2.12 respectively (p = 0.03). Median TTP was 7.7 and 6.4 months in patients showing increased FISH and CISH EGFR GCN whereas it was 2.9 and 3.1 months in those with low FISH and CISH EGFR GCN (p = 0.04 and 0.02 respectively). FISH and CISH EGFR GCN may both represent effective tools for a further patients selection in K-RAS wild-type colorectal cancer treated with cetuximab.
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