Shoji Hirokazu, Yamada Yasuhide, Taniguchi Hirokazu, Nagashima Kengo, Okita Natsuko, Takashima Atsuo, Honma Yoshitaka, Iwasa Satoru, Kato Ken, Hamaguchi Tetsuya, Shimada Yasuhiro
Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
Cancer Sci. 2014 Aug;105(8):1002-7. doi: 10.1111/cas.12453. Epub 2014 Aug 7.
c-MET is implicated in the pathogenesis and growth of a wide variety of human malignancies, including colorectal cancer (CRC). The aim of the present study was to clarify the association between c-MET expression and tumor recurrence in CRC patients after curative liver resection, and to evaluate concordance in c-MET expression and various mutations of KRAS, BRAF and PIK3CA between primary CRC and paired liver metastases. A cohort of patients was tested for c-MET immunoreactivity (i.e. immunohistochemistry [IHC]) and KRAS, BRAF and PIK3CA mutations. Analyses were performed both on primary tumors and paired liver metastases, and the association between IHC and mutations results were assessed. A total of 108 patients were eligible. A total of 53% of patients underwent simultaneous resection of primary tumors and metastases, and the others underwent metachronous resection. Levels of concordance between primary tumors and metastases were 65.7%, 87.7%, 100% and 95.2% for c-MET, KRAS, BRAF and PIK3CA, respectively. High levels of c-MET expression (c-MET-high) in the primary tumors were observed in 52% of patients. Relapse-free survival was significantly shorter for patients with c-MET-high primary tumors (9.7 months) than for those with c-MET-low primary tumors (21.1 months) (P = 0.013). These results suggest that a high level of genetic concordance in KRAS, BRAF and PIK3CA between primary tumors and liver metastases, and c-MET-high in the primary tumors were associated with shorter relapse-free survival after hepatic metastasectomy.
c-MET与包括结直肠癌（CRC）在内的多种人类恶性肿瘤的发病机制和生长有关。本研究的目的是阐明c-MET表达与CRC患者根治性肝切除术后肿瘤复发之间的关联，并评估原发性CRC与配对肝转移灶之间c-MET表达以及KRAS、BRAF和PIK3CA各种突变的一致性。对一组患者进行了c-MET免疫反应性检测（即免疫组织化学[IHC]）以及KRAS、BRAF和PIK3CA突变检测。对原发性肿瘤和配对肝转移灶均进行了分析，并评估了IHC与突变结果之间的关联。共有108例患者符合条件。共有53%的患者同时切除了原发性肿瘤和转移灶，其余患者接受了异时性切除。原发性肿瘤和转移灶之间c-MET、KRAS、BRAF和PIK3CA的一致性水平分别为65.7%、87.7%、100%和95.2%。52%的患者原发性肿瘤中观察到高水平的c-MET表达（c-MET高表达）。c-MET高表达原发性肿瘤患者的无复发生存期（9.7个月）明显短于c-MET低表达原发性肿瘤患者（21.1个月）（P = 0.013）。这些结果表明，原发性肿瘤与肝转移灶之间KRAS、BRAF和PIK3CA的高度基因一致性以及原发性肿瘤中的c-MET高表达与肝转移切除术后较短的无复发生存期相关。
