对西妥昔单抗治疗的KRAS野生型结直肠癌患者进行疗效评估及随访,收集每例患者的癌组织标本及临床病理资料,检测每例患者BRAF、PIK3CA基因的突变情况,采用免疫组织化学染色检测PTEN在癌及癌旁组织中的表达情况.结果显示,KRAS、BRAF及PIK3CA基因均为野生型的患者对单抗治疗的反应率为62.5%(CR+PR),而存在BRAF及PIK3CA突变患者的反应率分别为0,28.6%,证实BRAF及PIK3CA的突变可显著影响西妥昔单抗(C225)的疗效.PTEN主要表达在细胞核内,在癌组织中表达降低或缺失,在正常组织中表达正常,并且PTEN的表达与C225的疗效密切相关,PTEN表达阳性及阴性患者的反应率(CR+PR)分别为42.9%,36.4%(P＜0.05).BRAF、PIK3CA的突变和PTEN的表达缺失可以显著影响C225的疗效.

Colorectal cancer patients with wild-type KRAS were collected and treated with cetuximab and the efficacy was assessed. Paraffin-embedded tumor specimes and clinicopathological parameters were collected and mutations of BRAF and PIK3CA were checked. The PTEN expression status was detected through immunohistochemistry. The study indicates that the objective response rate of patients with wild-type BRAF and PIK3CA is 62.5% (CR+PR). In contrast, the objective response rate of patients with mutation-type BRAF and PIK3CA are 0% and 28.6%, respectively. Therefore, the fact that BRAF and PIK3CA mutations could affect the effective of cetuximab is deducted. And PTEN expression is mainly located in cell nucleus and PTEN expression is associated with the response to cetuximab significantly. The objective response rate of patients with PTEN expression or null are 42.9% and 36.4% (P<0.05), respectively. In conclusion, BRAF, PIK3CA mutations and PTEN expression null both have been associated with resistance to cetuximab. BRAF, PIK3CA, and PTEN could serve as the predictive bio-markers for the response to cetuximab.