Kishiki Tomokazu, Ohnishi Hiroaki, Masaki Tadahiko, Ohtsuka Kouki, Ohkura Yasuo, Furuse Jyunji, Sugiyama Masanori, Watanabe Takashi
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.
Oncol Rep. 2014 Jul;32(1):57-64. doi: 10.3892/or.2014.3179. Epub 2014 May 15.
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.
报告表明，即使在KRAS突变的结肠癌中，也有一部分患者能从抗表皮生长因子受体单克隆抗体（MoAb）治疗中获益。本研究的目的是确定有助于转移性结直肠癌（mCRC）对抗表皮生长因子受体MoAb产生反应的基因谱。我们根据KRAS突变亚型、BRAF和PIK3CA突变状态以及PTEN和MET表达，回顾性评估了抗表皮生长因子受体MoAb在KRAS突变的mCRC患者中的疗效。在21例KRAS突变肿瘤患者中，8例（38%）携带p.G13D突变，7例（33%）携带p.G12V突变，5例（24%）携带p.G12D突变，1例（5%）携带p.G12C突变。携带p.G13D突变的患者疾病控制率显著高于其他KRAS突变患者（P=0.042），且无进展生存期（PFS）有比其他KRAS突变患者更长的趋势，差异具有边缘显著性（P=0.074）。在KRAS突变患者中，PTEN缺失的患者PFS显著短于PTEN表达正常的患者（P=0.044）。与KRAS突变患者中MET正常表达相比，MET过表达与更短的PFS显著相关（P=0.016）。我们的数据证明了PTEN和MET表达改变作为KRAS突变的mCRC患者对抗表皮生长因子受体MoAbs反应的预测标志物的潜在效用。此外，我们证实了与其他KRAS突变相比，KRAS p.G13D突变对抗表皮生长因子受体治疗有更好反应的预测价值。
