Department of Medical Oncology, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen, HB 6500, The Netherlands.
Br J Cancer. 2011 Mar 15;104(6):1020-6. doi: 10.1038/bjc.2011.26. Epub 2011 Mar 1.
KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor antibody in metastatic colorectal cancer (CRC). KRAS mutation analysis is usually performed on primary tumour tissue because metastatic tissue is often not available. However, controversial data are available on the concordance of test results between primary tumours and corresponding metastases. We assessed the concordance of KRAS mutation status in a study of 305 primary colorectal tumours and their corresponding liver metastases.
Patients with histologically confirmed CRC who underwent surgical resection of the primary tumour and biopsy or surgical resection of the corresponding liver metastasis were included. KRAS mutation analysis was performed for codons 12 and 13.
KRAS mutation was detected in 108 out of 305 primary tumours (35.4%). In 11 cases (3.6%), we found a discordance between primary tumour and metastasis: 5 primary tumours had a KRAS mutation with a wild-type metastasis, 1 primary tumour was wild type with a KRAS mutation in the metastasis, and in 5 cases the primary tumour and the metastasis had a different KRAS mutation.
We observed a high concordance of KRAS mutation status of 96.4% (95% CI 93.6-98.2%) between primary colorectal tumours and their corresponding liver metastases. In only six patients (2.0%; 95% CI 0.7-4.2%), the discordance was clinically relevant. In this largest and most homogenous study to date, we conclude that both primary tumours and liver metastases can be used for KRAS mutation analysis.
KRAS 基因突变是转移性结直肠癌(CRC)患者对表皮生长因子受体抗体治疗产生耐药的一个负面预测因子。KRAS 基因突变分析通常在原发性肿瘤组织上进行,因为转移性组织通常无法获得。然而,关于原发性肿瘤和相应转移灶之间检测结果的一致性存在争议数据。我们评估了 305 例原发性结直肠肿瘤及其相应肝转移灶中 KRAS 基因突变状态的一致性。
纳入接受过原发性肿瘤手术切除和相应肝转移灶活检或手术切除的组织学证实为 CRC 的患者。对密码子 12 和 13 进行 KRAS 基因突变分析。
在 305 例原发性肿瘤中,有 108 例(35.4%)检测到 KRAS 基因突变。在 11 例(3.6%)中,我们发现原发性肿瘤和转移灶之间存在不一致性:5 例原发性肿瘤 KRAS 基因突变而转移灶野生型,1 例原发性肿瘤野生型而转移灶 KRAS 基因突变,5 例原发性肿瘤和转移灶有不同的 KRAS 基因突变。
我们观察到 96.4%(95%CI 93.6-98.2%)的原发性结直肠肿瘤与其相应肝转移灶之间 KRAS 基因突变状态具有高度一致性。只有 6 例患者(2.0%;95%CI 0.7-4.2%)的不一致性具有临床意义。在迄今为止最大和最同质的研究中,我们得出结论,原发性肿瘤和肝转移灶均可用于 KRAS 基因突变分析。