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.