Ålgars Annika, Sundström Jari, Lintunen Minnamaija, Jokilehto Terhi, Kytölä Soili, Kaare Milja, Vainionpää Reetta, Orpana Arto, Österlund Pia, Ristimäki Ari, Carpen Olli, Ristamäki Raija
Department of Oncology, Turku University Hospital, Hämeentie 11, Turku, 20521, Finland.
MediCity Research Laboratory, University of Turku, Tykistökatu 6 A, Turku, 20520, Finland.
Int J Cancer. 2017 Feb 15;140(4):922-929. doi: 10.1002/ijc.30507. Epub 2016 Nov 23.
Anti-EGFR antibodies are used for the treatment of RAS wild type metastatic colorectal cancer. We previously showed that EGFR gene copy number (GCN) predicts response to anti-EGFR therapy in KRAS exon 2 wild type metastatic colorectal cancer. The aim of our study was to analyse the predictive role of EGFR GCN in RAS/BRAF/PIK3CA wild type metastatic colorectal cancer. The material included 102 patients with KRAS exon 2 wild type metastatic colorectal cancer treated with anti-EGFR ± cytotoxic therapy. Next generation sequencing was used for KRAS, NRAS, BRAF and PIK3CA gene mutation analyses. EGFR GCN was analysed by EGFR immunohistochemistry guided automated silver in situ hybridisation. Increased EGFR GCN (≥4.0) predicted a better response and prolonged progression free survival in anti-EGFR treated RAS/BRAF/PIK3CA wild type patients (Log-rank test, p = 0.0004). In contrast, survival of RAS/BRAF/PIK3CA wild type, EGFR GCN below 4.0 patients did not differ from patients with mutant RAS, BRAF or PIK3CA. Our study indicates that EGFR GCN predicts anti-EGFR treatment efficacy in patients with RAS/BRAF/PIK3CA wt metastatic CRC. Tumours with EGFR GCN below 4.0 appear to be as refractory to anti-EGFR treatment as tumours with mutation in any of the RAS/RAF/PIK3CA pathway genes.
抗表皮生长因子受体（EGFR）抗体用于治疗RAS野生型转移性结直肠癌。我们之前的研究表明，EGFR基因拷贝数（GCN）可预测KRAS外显子2野生型转移性结直肠癌患者对抗EGFR治疗的反应。本研究旨在分析EGFR GCN在RAS/BRAF/PIK3CA野生型转移性结直肠癌中的预测作用。研究材料包括102例接受抗EGFR±细胞毒性治疗的KRAS外显子2野生型转移性结直肠癌患者。采用下一代测序技术对KRAS、NRAS、BRAF和PIK3CA基因进行突变分析。通过EGFR免疫组织化学引导的自动银原位杂交分析EGFR GCN。在接受抗EGFR治疗的RAS/BRAF/PIK3CA野生型患者中，EGFR GCN增加（≥4.0）预示着更好的反应和更长的无进展生存期（对数秩检验，p = 0.0004）。相比之下，RAS/BRAF/PIK3CA野生型、EGFR GCN低于4.0的患者的生存期与RAS、BRAF或PIK3CA突变的患者没有差异。我们的研究表明，EGFR GCN可预测RAS/BRAF/PIK3CA野生型转移性结直肠癌患者对抗EGFR治疗的疗效。EGFR GCN低于4.0的肿瘤似乎与RAS/RAF/PIK3CA通路中任何基因发生突变的肿瘤一样，对抗EGFR治疗具有难治性。
