m>EGFRm> gene copy number predicts response to anti-EGFR treatment in m>RASm> wild type and m>RASm>/m>BRAFm>/m>PIK3CAm> wild type metastatic colorectal cancer

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• 作者：Annika &Aring ; lgars ; Jari Sundstr&ouml ; m ; Minnamaija Lintunen ; Terhi Jokilehto ; Soili Kyt&ouml ; l&auml ; Milja Kaare ; Reetta Vainionp&auml ; &auml ; Arto Orpana ; Pia &Ouml ; sterlund ; Ari Ristim&auml ; ki ; Olli Carpen and Raija Ristam&auml ; ki
• 刊名：International Journal of Cancer
• 出版年：2017
• 出版时间：15 February 2017
• 年：2017
• 卷：140
• 期：4
• 页码：922-929
• 全文大小：291K
• ISSN：1097-0215

文摘

Anti-EGFR antibodies are used for the treatment of m>RASm> wild type metastatic colorectal cancer. We previously showed that m>EGFRm> gene copy number (GCN) predicts response to anti-EGFR therapy in m>KRASm> exon 2 wild type metastatic colorectal cancer. The aim of our study was to analyse the predictive role of m>EGFRm> GCN in m>RAS/BRAF/PIK3CAm> wild type metastatic colorectal cancer. The material included 102 patients with m>KRASm> exon 2 wild type metastatic colorectal cancer treated with anti-EGFR ± cytotoxic therapy. Next generation sequencing was used for m>KRASm>, m>NRASm>, m>BRAFm> and m>PIK3CAm> gene mutation analyses. m>EGFRm> GCN was analysed by EGFR immunohistochemistry guided automated silver m>in situm> hybridisation. Increased m>EGFRm> GCN (≥4.0) predicted a better response and prolonged progression free survival in anti-EGFR treated m>RAS/BRAF/PIK3CAm> wild type patients (Log-rank test, m>pm> = 0.0004). In contrast, survival of m>RAS/BRAF/PIK3CAm> wild type, m>EGFRm> GCN below 4.0 patients did not differ from patients with mutant m>RASm>, m>BRAFm> or m>PIK3CAm>. Our study indicates that m>EGFRm> GCN predicts anti-EGFR treatment efficacy in patients with m>RAS/BRAF/PIK3CAm> wt metastatic CRC. Tumours with m>EGFRm> GCN below 4.0 appear to be as refractory to anti-EGFR treatment as tumours with mutation in any of the m>RAS/RAF/PIK3CAm> pathway genes.