Impact of genetic profiles on the efficacy of anti-EGFR antibodies in metastatic colorectal cancer with KRAS mutation

Kishiki,Tomokazu; Ohnishi,Hiroaki; Masaki,Tadahiko; Ohtsuka,Kouki; Ohkura,Yasuo; Furuse,Jyunji; Sugiyama,Masanori; Watanabe,Takashi

doi:10.3892/or.2014.3179

Impact of genetic profiles on the efficacy of anti-EGFR antibodies in metastatic colorectal cancer with KRAS mutation

Authors:
- Tomokazu Kishiki
- Hiroaki Ohnishi
- Tadahiko Masaki
- Kouki Ohtsuka
- Yasuo Ohkura
- Jyunji Furuse
- Masanori Sugiyama
- Takashi Watanabe
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Affiliations: Department of Surgery, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan, Department of Laboratory Medicine, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan, Department of Pathology, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan, Department of Medical Oncology, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan
Published online on: May 15, 2014 https://doi.org/10.3892/or.2014.3179
Pages: 57-64

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Abstract

Reports indicate that, even in KRAS-mutated colon cancer, there are subsets of patients who benefit from anti-EGFR monoclonal antibody (MoAb) treatment. The aim of the present study was to identify genetic profiles that contribute to the responsiveness of metastatic colorectal cancer (mCRC) to anti-EGFR MoAb. We retrospectively evaluated the efficacy of anti-EGFR MoAb in mCRC patients with KRAS mutations according to KRAS mutational subtypes, BRAF and PIK3CA mutational status and PTEN and MET expression. Among 21 patients with KRAS-mutant tumors, 8 (38%) harbored p.G13D, 7 (33%) harbored p.G12V, 5 (24%) harbored p.G12D, and 1 (5%) harbored p.G12C mutation. Patients with the p.G13D mutation exhibited a significantly higher disease control rate than patients with other KRAS mutations (P=0.042), and tended to show a longer progression-free survival (PFS) than patients with other KRAS mutations with marginal significance (P=0.074). Patients with loss of PTEN had significantly shorter PFS than those with normal PTEN expression in patients with KRAS mutations (P=0.044). MET overexpression was significantly associated with shorter PFS compared to normal MET expression in patients with KRAS mutations (P=0.016). Our data demonstrated the potential utility of alterations in PTEN and MET expression as predictive markers for response to anti-EGFR MoAbs in mCRC patients with KRAS mutations. In addition, we confirmed the predictive value of the KRAS p.G13D mutation for better response to anti-EGFR therapies in comparison with other KRAS mutations.

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