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EGFR gene copy number predicts response to anti‐EGFR treatment in RAS wild type and RAS / BRAF / PIK3CA wild type metastatic colorectal cancer
Author(s) -
Ålgars Annika,
Sundström Jari,
Lintunen Minnamaija,
Jokilehto Terhi,
Kytölä Soili,
Kaare Milja,
Vainionpää Reetta,
Orpana Arto,
Österlund Pia,
Ristimäki Ari,
Carpen Olli,
Ristamäki Raija
Publication year - 2016
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30507
Subject(s) - wild type , copy number variation , biology , cancer research , gene dosage , colorectal cancer , gene , oncology , medicine , genetics , cancer , gene expression , genome , mutant
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.