Department of Surgery, Division of Experimental Therapy, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Br J Cancer. 2011 Jul 12;105(2):281-7. doi: 10.1038/bjc.2011.184. Epub 2011 Jun 14.
Understanding the molecular biology of colorectal cancer (CRC) provides opportunities for effective personalised patient management. We evaluated whether chromosomal aberrations, mutations in the PI(3)K signalling pathway and the CpG-island methylator phenotype (CIMP) in primary colorectal tumours can predict liver metastases.
Formalin-fixed paraffin-embedded material from primary colorectal tumours of three different groups were investigated: patients with CRC without metastases (M0, n=39), patients who were treated with hyperthermal intraperitoneal chemotherapy for CRC metastases confined to the peritoneum (PM, n=46) and those who had isolated hepatic perfusion for CRC metastases confined to the liver (LM, n=48).
All samples were analysed for DNA copy number changes, PIK3CA, KRAS, BRAF mutations, CIMP and microsatellite instability. The primary CRCs of the LM group had significantly higher frequency of amplified chromosome 20q (P=0.003), significantly fewer mutations in the PI(3)K signalling pathway (P=0.003) and fewer CIMP high tumours (P=0.05). There was a strong inverse correlation between 20q and the PI(3)K pathway mutations.
The development of CRC liver metastases is associated with amplification of chromosome 20q and not driven by mutations in the PI(3)K signalling pathway.
了解结直肠癌（CRC）的分子生物学为有效的个性化患者管理提供了机会。我们评估了原发性结直肠肿瘤中的染色体异常、PI(3)K 信号通路突变和 CpG 岛甲基化表型（CIMP）是否可以预测肝转移。
对三组不同患者的原发性结直肠肿瘤的福尔马林固定石蜡包埋材料进行了研究：无转移的 CRC 患者（M0，n=39）、局限于腹膜的 CRC 转移接受高温腹腔内化疗的患者（PM，n=46）和局限于肝脏的 CRC 转移接受肝灌注的患者（LM，n=48）。
所有样本均进行了 DNA 拷贝数变化、PIK3CA、KRAS、BRAF 突变、CIMP 和微卫星不稳定性分析。LM 组的原发性 CRC 中，20q 染色体扩增的频率明显更高（P=0.003），PI(3)K 信号通路的突变明显更少（P=0.003），CIMP 高肿瘤也更少（P=0.05）。20q 与 PI(3)K 通路突变之间存在强烈的负相关。
CRC 肝转移的发展与 20q 染色体扩增有关，而不是由 PI(3)K 信号通路突变驱动。
